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Encyclopedia > Ketamine
Ketamine
Systematic (IUPAC) name
2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one
Identifiers
CAS number 6740-88-1
ATC code N01AX03 N01AX14
PubChem 3821
DrugBank APRD00493
Chemical data
Formula C13H16ClNO 
Mol. mass 237.725 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life 2.5-3 hours.
Excretion renal (>90%)
Therapeutic considerations
Pregnancy cat.

B Image File history File links Download high-resolution version (1100x1017, 59 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Ketamine ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, symbol, number chlorine, Cl, 17 Chemical series halogens Group, period, block 17, 3, p Appearance yellowish green Standard atomic weight 35. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) pale blue (liquid) Standard atomic weight 15. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... It has been suggested that Effective half-life be merged into this article or section. ... The kidneys are important excretory organs in vertebrates. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...

Legal status

Schedule I(CA) Class C(UK) Schedule III(US) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... Motto (Latin for From Sea to Sea) Anthem O Canada Royal anthem: God Save the Queen Capital Ottawa Largest city Toronto Official languages English, French Government Parliamentary democracy and federal constitutional monarchy  -  Monarch Queen Elizabeth II  -  Governor General Michaëlle Jean  -  Prime Minister Stephen Harper Establishment  -  Act of Union February... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...

Routes IV, IM, Insufflated, oral, topical

Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist,[1] and, like other drugs of this class such as tiletamine, and phencyclidine (PCP), induces a state referred to as "dissociative anesthesia."[2] As with other pharmaceuticals of this type, ketamine is used illicitly as a recreational drug, sometimes referred to as Special K. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Intravenous therapy or IV therapy is the giving of liquid substances directly into a vein. ... Intramuscular injection is the injection of a substance directly into a muscle. ... Wikipedia does not yet have an article with this exact name. ... In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, nasopharynx, or the eye. ... A dissociative is a drug which reduces (or blocks) signals to the conscious mind from other parts of the brain, typically, but not necessarily, or limited to the physical senses. ... Anesthesia (AE), also anaesthesia (BE), is the process of blocking the perception of pain and other sensations. ... In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (mostly amines). ... Pharmacology (in Greek: pharmakon (φάρμακον) meaning drug, and lego (λέγω) to tell (about)) is the study of how drugs interact with living organisms to produce a change in function. ... NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the NMDA receptor (NMDAR). ... Tiletamine, 2-ethylamino-2-(2-thienyl) cyclohexanone Tiletamine is a dissociative anesthetic chemically and pharmacologically related to other anesthetics in this family such as ketamine and phencyclidine. ... “Angel Dust” redirects here. ... A dissociative is a drug which reduces (or blocks) signals to the conscious mind from other parts of the brain, typically, but not necessarily, or limited to the physical senses. ... Recreational drug use is the use of psychoactive drugs for recreational rather than medical or spiritual purposes, although the distinction is not always clear. ... This article is about the food. ...


Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucinations, neurotoxicity [citation needed], arterial hypertension, and bronchodilation.[citation needed] It is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. It is also a popular anesthetic in veterinary medicine. For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Anesthesia or anaesthesia (see spelling differences) has traditionally meant the condition of having the perception of pain and other sensations blocked. ... A hallucination is a sensory perception experienced in the absence of an external stimulus, as distinct from an illusion, which is a misperception of an external stimulus. ... Neurotoxicity occurs when the exposure to natural or manmade toxic substances ,which are called neurotoxins, alters the normal activity of the nervous system. ... Arterial hypertension, or high blood pressure is a medical condition where the blood pressure is chronically elevated. ... A bronchodilator is a medication intended to improve bronchial airflow. ... This article or section may be confusing for some readers, and should be edited to be clearer. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Intensive care medicine or critical care medicine is concerned with providing greater than ordinary medical care and observation to people in a critical or unstable condition. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Bronchospasm is a difficulty in breathing caused by a sudden constriction of the muscles in the walls of the bronchioles. ... Veterinary medicine is the application of medical, diagnostic, and therapeutic principles to companion, domestic, exotic, wildlife, and production animals. ...


Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic; however, some brands reportedly have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, S-Ketamine, is also available for medical use under the brand name Ketanest S.[3] The term chiral (pronounced ) is used to describe an object which is non-superimposable on its mirror image. ... In chemistry, a racemate is a mixture of equal amounts of left- and right-handed stereoisomers of a chiral molecule. ... In chemistry, enantiomers (from the Greek ἐνάντιος, opposite, and μέρος, part or portion) are stereoisomers that are nonsuperimposable complete mirror images of each other, much as ones left and right hands are the same but opposite. ...

Contents

History

Ketamine was first reported in 1962 as part of an effort to find a safer anaesthetic alternative to Phencyclidine (PCP), which was more likely to cause hallucinations, neurotoxicity and seizures. The drug was first given to American soldiers during the Vietnam War. It is still widely used in humans. There may be some evidence that Ketamine has the potential to cause emergence phenomena because of the drug's possible psychotomimetic effects.[citation needed] It is also used widely in veterinary medicine, or as a battlefield anaesthetic in developing nations.[4] “Angel Dust” redirects here. ... A hallucination is a sensory perception experienced in the absence of an external stimulus, as distinct from an illusion, which is a misperception of an external stimulus. ... Neurotoxicity occurs when the exposure to natural or manmade toxic substances ,which are called neurotoxins, alters the normal activity of the nervous system. ... This article is about epileptic seizures. ... Combatants Republic of Vietnam United States Republic of Korea Thailand Australia New Zealand The Philippines National Front for the Liberation of South Vietnam Democratic Republic of Vietnam People’s Republic of China Democratic Peoples Republic of Korea Strength US 1,000,000 South Korea 300,000 Australia 48,000... Describes the actions of a drug in producing symptoms of psychosis including delusions and/or hallucinations. ... Veterinary medicine is the application of medical, diagnostic, and therapeutic principles to companion, domestic, exotic, wildlife, and production animals. ... An illustration showing a variety of wounds from the Feldbuch der Wundarznei (Field manual for the treatment of wounds) by Hans von Gersdorff, (1517). ...


Ketamine's side effects eventually made it a popular psychedelic in 1965. The drug was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of John Lilly's The Scientist and Marcia Moore and Howard Alltounian's Journeys into the Bright World, which documented the unusual phenomenology of ketamine intoxication. This entry pertains to the word psychedelic, its origin and uses. ... Psychiatry is a branch of medicine dealing with the prevention, assessment, diagnosis, treatment, and rehabilitation of the mind and mental illness. ... John Cunningham Lilly (January 6, 1915 – September 30, 2001) was an American physician, psychoanalyst and writer. ...


The incidence of recreational ketamine use increased through the end of the century, especially in the context of raves and other parties. The increase in illicit use prompted ketamine's placement in Schedule III of the United States Controlled Substance Act in August 1999.[5] In the United Kingdom, it became outlawed and labelled a Class C drug on January 1, 2006.[6] In Canada ketamine is classified as a Schedule I narcotic.[7] In Hong Kong, as of year 2000, Ketamine is regulated under Schedule 1 of Hong Kong Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals, for university research purposes, or with a physician's prescription.[8] This article does not cite its references or sources. ... A rave party, more often called a rave, is an all-night dance event where DJs and other performers play electronic dance music and rave music. ... The Controlled Substances Act (CSA), Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, is the legal foundation of the United States governments fight against the abuse of drugs and other substances. ... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... is the 1st day of the year in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ...


Medical use

10 ml bottles of Ketamine
Contraindications:
Side effects:

Severe: Impairs all senses, especially: Download high resolution version (1600x1200, 113 KB)Ketamine in 10ml bottles Source: USDOJ File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... Download high resolution version (1600x1200, 113 KB)Ketamine in 10ml bottles Source: USDOJ File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... In medicine, a contraindication is a condition or factor that increases the risk involved in using a particular drug, carrying out a medical procedure or engaging in a particular activity. ... This article does not cite any references or sources. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Stimulants are drugs that temporarily increase alertness and wakefulness. ... An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...

  • Sight
  • Balance
  • Sense of time

Cardiovascular: The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ...

  • Partial depressant

Gastrointestinal: For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and...

Musculoskeletal: For other uses, see Nausea (disambiguation). ... A top-down view of skeletal muscle Muscle (from Latin musculus little mouse [1]) is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. ... Skeleton is also a winter sport: see skeleton (sport). ...

  • Relaxant

Neurological: Neurology is a branch of medicine dealing with disorders of the central and peripheral nervous systems. ...

Respiratory: For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... In animal physiology, respiration is the transport of oxygen from the ambient air to the tissue cells and the transport of carbon dioxide in the opposite direction. ...

  • Partial depressant/stimulant

In medical settings, Ketamine is usually injected intravenously or intramuscularly,[9] but it is also effective when insufflated, smoked, or taken orally.[10] Intramuscular injection is an injection of a substance directly into a muscle. ...


Since it suppresses breathing much less than most other available anaesthetics,[11] ketamine is still used in human medicine as a first-choice anaesthetic for victims with unknown medical history (e.g. from traffic accidents), in podiatry and other minor surgery, and occasionally for the treatment of migraine. There is ongoing research in France, Russia, and the U.S. into the drug's usefulness in pain therapy, depression suppression, and for the treatment of alcoholism[12] and heroin addiction.[13] A car accident in Yate, near Bristol, England, in July 2004. ... Podiatry, more appropriately podiatric medicine is a field of healthcare devoted to the study and treatment of disorders of the foot, ankle, and sometimes knee, leg and hip (collectively known as the lower extremity). ... “Surgeon” redirects here. ... Alcoholism is the consumption of, or preoccupation with, alcoholic beverages to the extent that this behavior interferes with the drinkers normal personal, family, social, or work life, and may lead to physical or mental harm. ... For other uses, see Heroin (disambiguation). ... For other uses, see addicted. ...


In veterinary anesthesia, ketamine is often used for its anaesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals. Veterinarians often use ketamine with sedative drugs to produce balanced anaesthesia and analgesia, and as a constant rate infusion to help prevent pain wind-up. Ketamine is used to manage pain among large animals, though it has less effect on bovines. It is the primary intravenous anaesthetic agent used in equine surgery, often in conjunction with detomidine and thiopental, or sometimes Glyceryl guaiacolate. Veterinary anesthesia is anesthesia performed on animals (excluding humans) performed by a veterinarian. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... For other uses, see Rabbit (disambiguation). ... Species 50 species; see text *Several subfamilies of Muroids include animals called rats. ... Tribes Bovini Boselaphini Strepsicerotini The biological subfamily Bovinae includes a diverse group of about 24 medium-sized to large ungulates, including domestic cattle, bison, the Water Buffalo, the Yak, and the four-horned and spiral-horned antelopes. ... Anesthesia (AE), also anaesthesia (BE), is the process of blocking the perception of pain and other sensations. ... An imidazoline derivative alpha2-adrenergic agonist, used as a large animal sedative,primarily used in horses. ... Sodium thiopental (also called sodium pentothal (™ of Abbott Laboratories), thiopental (or thiopentone) sodium) is a rapid-onset, short-acting barbiturate general anesthetic. ...


Ketamine may be used in small doses (0.1–0.5 mg/kg/h) as a local anesthetic, particularly for the treatment of pain associated with movement and neuropathic pain.[14] It has the added benefit of counter-acting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines.[15] Ketamine is a co-analgesic, and so is most effective when used alongside a low-dose opioid; while it does have analgesic effects by itself, the higher doses required can cause disorientating side effects.[15] The combination of ketamine with an opioid is, however, particularly useful for pain caused by cancer.[16] Neuropathy is a disease of the peripheral nervous system. ... In neurobiology, sensitization is the progressive amplification of a response following repeated administrations of a stimulus (Bell et al. ... Chronic pain was originally defined as pain that has lasted 6 months or longer. ... An assortment of psychoactive drugs A psychoactive drug or psychotropic substance is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. ... Alprazolam 2mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered as minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are brought on by slowing down the central nervous system. ... An opioid is a chemical substance that has a morphine-like action in the body. ...


The effect of Ketamine on the respiratory and circulatory systems is different from that of other anaesthetics. When used at anaesthetic doses, it will usually stimulate rather than depress the circulatory system.[17] It is sometimes possible to perform ketamine anaesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in sub-anaesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.[15] The Respiratory System Among four-legged animals, the respiratory system generally includes tubes, such as the bronchi, used to carry air to the lungs, where gas exchange takes place. ... For transport in plants, see Vascular tissue. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... A psychoactive drug or psychotropic substance is a chemical that alters brain function, resulting in temporary changes in perception, mood, consciousness, or behaviour. ... This article discusses the term God in the context of monotheism and henotheism. ... Alprazolam 2mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered as minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are brought on by slowing down the central nervous system. ...


Low-dose ketamine is recognized for its potential effectiveness in the treatment of complex regional pain syndrome (CRPS), according to a retrospective review published in the October 2004 issue of Pain Medicine.[18] Although low-dose ketamine therapy is established as a generally safe procedure, reported side effects in some patients have included hallucinations, dizziness, lightheadedness and nausea. Therefore nurses administering ketamine to patients with CRPS should only do so in a setting where a trained physician is available if needed to assess potential adverse effects on patients.[19] Complex Regional Pain Syndrome (CRPS) is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. ... Complex Regional Pain Syndrome (CRPS) is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. ...


Experimental antidepressant use

When treating patients suffering from complex regional pain syndrome (CRPS) with a low-dose (subanesthetic) ketamine infusion, it was observed that some patients made a significant recovery from associated depression. This recovery was not formally documented, as the primary concern was the treatment of the patient's pain. Needless to say, it was not possible to quantify to what degree depression recovery was secondary to the patient's recovery from CRPS. Based on this result, it was thought that a low-dose (subanesthetic) infusion of ketamine was worth a trial in patients who were suffering from treatment-resistant depression without other physical or psychiatric illness.


Correll et al. gave ketamine intravenously to patients commencing at 15–20 mg/h (0.1–0.2 mg/kg/h) and the dose increased until a maximum tolerated dose was achieved. This dose was assumed to be a therapeutic dose and was maintained for 5 days. Patients were able to eat, drink, watch television, or read. They could feel inebriated and/or unsteady when walking. If hallucinations occurred, the dose was to be reduced. The patient's normal medications were continued as it was feared that stopping them may result in a severe depressive episode. Before and following each treatment with ketamine, at patient clinic visits, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Score (HAMD-17) were obtained. Two of the patients were described with impressive improvement in depression being maintained for 12 months in patient A and recurrence at 2.5 months and 9 months in patient B.[20]


The National Institute of Health News reports that a study of 18 patients has found that ketamine significantly improved treatment-resistant major depression within hours of injection.[21] The improvement lasted up to one week after the single dose.[22] The patients in the study were previously treatment resistant, having tried an average of six other treatments that failed. NIMH director Dr. Thomas Insel said in the paper: The National Institutes of Health is an institution of the United States government which focuses on medical research. ...


"To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients."


The researchers apparently attribute the effect to ketamine being an NMDA receptor antagonist.[23] Those findings of Zarate et al corroborate earlier findings by Berman et al.[24] However Zarate et al do rise some concerns about their results due to a possible lack of blinding, because of the ebriating effects of low dose Ketamine infusion, and it is recommended that future studies shall include an active placebo. The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA (N-methyl d-aspartate) is a name of its selective specific agonist). ... Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling. ...


The findings by Zarate et al. are confirmed by Liebrenz et al, who substantially helped a 55-year-old male subject with a treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence by giving an intravenous infusion of 0.5 mg/kg ketamine over a period of 50 minutes and Goforth et al who helped a patient with severe, recurrent major depressive disorder that demonstrated marked improvement within 8 hours of receiving a preoperative dose of ketamine and 1 treatment of electroconvulsive therapy with bitemporal electrode placement.[25][26]


However, a new study in mice by Zarate et al. shows that blocking the NMDA receptor is an intermediate step. According to this study, blocking NMDA increases the activity of another receptor, AMPA, and this boost in AMPA activity is crucial for ketamine’s rapid antidepressant actions. NMDA and AMPA are receptors for the neurotransmitter glutamate. The glutamate system has been implicated in depression recently. This is a departure from previous thinking, which had focused on serotonin and norepinephrine. The glutamate system may represent a new avenue for treatment and research[27].


Krystal et al. retrospectively compared the seizure duration, ictal EEG, and cognitive side effects of ketamine and methohexital anesthesia with ECT in 36 patients.[28] Ketamine was well tolerated and prolonged seizure duration overall, but particularly in those who had a seizure duration shorter than 25 seconds with methohexital at the maximum available stimulus intensity. Ketamine also increased midictal EEG slow-wave amplitude. Thus, a switch to ketamine may be useful when it is difficult to elicit a robust seizure. Faster post-treatment reorientation with ketamine may suggest a lower level of associated cognitive side effects.


Kudoh et al. investigated whether ketamine is suitable for depressed patients who had undergone orthopedic surgery.[29] They studied 70 patients with major depression and 25 patients as the control (Group C). The depressed patients were divided randomly into two groups; patients in Group A, initial HAMD 12,7(n = 35) were induced with propofol, fentanyl, and ketamine and patients in Group B, initial HAMD 12,3 (n = 35) were induced with propofol and fentanyl. Depressed mood, suicidal tendencies, somatic anxiety, and hypochondriasis significantly decreased in Group A as compared with Group B. The group receiving ketamine also had significantly lower postoperative pain.


Treatment of addiction

The Russian doctor Evgeny Krupitsky (Clinical Director of Research for the Saint Petersburg Regional Center for Research in Addiction and Psychopharmacology) has gained encouraging results by using ketamine as part of a treatment for alcohol addiction which combines psychedelic and aversive techniques.[30][31] This method involved psychotherapy, controlled ketamine use and group therapy, and resulted in 60 of the 86 alcoholic males selected for the study remaining fully abstinent through one year of treatment. He has also treated heroin addicts and reached the conclusion that that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence from heroin during one year withhout any adverse reactions. In a recently published study 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, (with a single im injection of 2 mg/kg Ketamine) with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.[32][33]


Jovaisa et al from Lithuania demonstrated attenuation of opiate withdrawal symptoms with Ketamine. A total of 58 opiate-dependent patients were enrolled in a randomized, placebo-controlled, double-blind study. Patients underwent rapid opiate antagonist induction under general anesthesia. Prior to opiate antagonist induction patients were given either placebo (normal saline) or subanesthetic ketamine infusion of 0.5 mg/kg/h.Ketamine group presented better control of withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant differences between Ketamine and Control groups were noted in anesthetic and early postanesthetic phases. There were no differences in effects on outcome after 4 months.[13]


Treatment of reflex sympathetic dystrophy

Ketamine is being used as a experimental and controversial treatment for Complex Regional Pain Syndrome (CRPS) also known as Reflex Sympathetic Dystrophy (RSD). CRPS/RSD is a severe chronic pain condition characterized by sensory, autonomic, motor and dystrophic signs and symptoms. The pain in CRPS is continuous, it worsens over time, and it is usually disproportionate to the severity and duration of the inciting event. The hypothesis is that ketamine manipulates NMDA receptors which might reboot aberrant brain activity. Complex Regional Pain Syndrome (CRPS) is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. ... Complex Regional Pain Syndrome (CRPS) is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. ... Complex Regional Pain Syndrome (CRPS) is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. ... Anatomy and Physiology of the A.N.S. In contrast to the voluntary nervous system, the involuntary or autonomic nervous system is responsible for homeostasis, maintaining a relatively constant internal environment by controlling such involuntary functions as digestion, respiration, and metabolism, and by modulating energy needed to cope with stressful... NMDA (N-methyl-D-aspartic acid) is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor. ...


There are two treatment modalities, the first consist of a low dose ketamine infusion of between 25-90 mg per day, over five days either in hospital or as an outpatient. This is called the awake technique. Open label, prospective, pain journal evaluation of a 10-day infusion of intravenous ketamine (awake technique) in the CRPS patient concluded that "A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation".[34]


Case notes of 33 patients whose CRPS pain was treated by the inpatient administration of a continuous subanesthetic intravenous infusion of ketamine were reviewed at Mackay Base Hospital, Queensland, Australia. A total of 33 patients with diagnoses of CRPS who had undergone ketamine treatment at least once were identified. Due to relapse, 12 of 33 patients received a second course of therapy, and two of 33 patients received a third. There was complete pain relief in 25 (76%), partial relief in six (18%), and no relief in two (6%) patients. The degree of relief obtained following repeat therapy (N=12) appeared even better, as all 12 patients who received second courses of treatment experienced complete relief of their CRPS pain. The duration of relief was also impressive, as was the difference between the duration of relief obtained after the first and after the second courses of therapy. In this respect, following the first course of therapy, 54% of 33 individuals remained pain free for >/=3 months and 31% remained pain free for >/=6 months. After the second infusion, 58% of 12 patients experienced relief for >/=1 year, while almost 33% remained pain free for >3 years. The most frequent side effect observed in patients receiving this treatment was a feeling of inebriation. Hallucinations occurred in six patients. Less frequent side effects also included complaints of light-headedness, dizziness, and nausea. In four patients, an alteration in hepatic enzyme profile was noted; the infusion was terminated and the abnormality resolved thereafter. No long-term side-effects were noted.[35]


The second treatment modality consists of putting the patient into a medically-induced coma and given an extremely high dosage of ketamine; typically between 600-900 mg.[36] This version, currently not allowed in the United States, is most commonly done in Germany but some treatments are now also taking place in Monterey, Mexico. According to Dr Schwartzman, 14 cases out of 41 patients in the coma induced ketamine experiments were completely cured. "We haven't cured the original injury," he says, "but we have cured the RSD or kept it in remission. The RSD pain is gone." "No one ever cured it before," he adds. "In 40 years, I have never seen anything like it. These are people who were disabled and in horrible pain. Most were completely incapacitated. They go back to work, back to school, and are doing everything they used to do. Most are on no medications at all. I have taken morphine pumps out of people. You turn off the pain and reset the whole system."[36] In Tuebingen, Germany Dr Kiefer treated a patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3-5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. On the second day, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment.[37]


Pharmacological model of schizophrenia

Ketamine and other NMDA antagonists such as PCP and MK-801 are considered to be the best available pharmacological models of schizophrenia to date. Unlike amphetamines, which influenced the synthesis of the "dopamine hypothesis of schizophrenia", ketamine can reliably produce the negative symptoms (social withdrawal, alogia), positive symptoms (hallucinations, delusions) and cognitive deficits of schizophrenia in healthy and schizophrenic humans, as well as in animal models of the illness. This has led to the development of the alternative "NMDA hypothesis of schizophrenia" which posits that the aetiology of schizophrenia results from NMDA receptor hypofunction, particularly in the prefrontal cortex. NMDA receptors in the prefrontal cortex modulate subcortical dopamine neurotransmission, whose hyperactivity is believed to produce the positive symptoms of schizophrenia. Disruption of the prefrontal cortex may also manifest the negative symptoms and cognitive deficits in schizophrenia. As disturbances in working memory, attention and executive functioning are consistently seen in schizophrenics and their healthy relatives, it is proposed that cognitive deficits in schizophrenia are the core of the disorder.


Neuropharmacology

Ketamine, like Phencyclidine, is primarily a non-competitive antagonist of the NMDA receptor,[1] which opens in response to binding of the neurotransmitter glutamate. This NMDA receptor mediates the analgesic (reduction of pain) effects of ketamine at low doses.[38] Evidence for this is reinforced by the fact that naloxone, an opioid antagonist, does not reverse the analgesia. Studies also seem to indicate that ketamine is 'use dependent' meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor.[38] “Angel Dust” redirects here. ... NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the NMDA receptor (NMDAR). ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ... Glutamate is the anion of glutamic acid. ... NMDA (N-methyl-D-aspartic acid) is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. ... An opioid is a chemical substance that has a morphine-like action in the body. ...


At high, fully anesthetic level doses, ketamine has also been found to bind to opioid mu receptors and sigma receptors.[38] Thus, loss of consciousness that occurs at high doses may be partially due to binding at the opioid mu and sigma receptors.[38] An opioid is a chemical substance that has a morphine-like action in the body. ...


Ketamine is racemic, and its R and S stereoisomers have different binding affinities: (S)-Ketamine has about four times greater affinity for the PCP site of the NDMA receptor than does (R)-Ketamine (in guinea pig brain).[38] (S)-ketamine seems to induce drowsiness more strongly than the (R) enantiomer; it is probable that (R)-ketamine is the stronger sigma agonist and so this enantiomer is likely to be responsible for the lowering of the seizure threshold that can occur with ketamine.[38] Since (S)-ketamine has greater analgesic effects and less hallucinogenic side effects than (R)-ketamine, the pure (S) enantiomer is sometimes preferred to the racemic mix for use in medical procedures, especially when lower doses are used for minor surgical procedures where the patient remains conscious during the operation. [39] In chemistry, a racemate is a mixture of equal amounts of left- and right-handed stereoisomers of a chiral molecule. ... ...

The effects seem to take place mainly in the hippocampal formation and in the prefrontal cortex. This evidence, along with the NMDA receptor's connection with the memory formation process, explains ketamine's profound effects on memory and thought. These effects inhibit the filtering function of the brain and may mirror the sensory overload associated with schizophrenia and near death experiences.[citation needed] Image File history File links Download high-resolution version (929x1100, 45 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Ketamine ... A skeletal formula is a three-dimensional model of the molecule that demonstrates the molecular shape, including bond angles. ... Image File history File links Download high-resolution version (974x1100, 184 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Ketamine ... armchair conformational isomerism of Cyclohexane. ... Image File history File links Download high-resolution version (927x1100, 52 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Ketamine ... Image File history File links Download high-resolution version (1100x785, 186 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Ketamine ... The hippocampus is structurally located inside the medial temporal lobe of the brain. ... “Prefrontal” redirects here. ... For other uses, see Memory (disambiguation). ... A near-death experience (NDE) is the perception reported by a person who nearly died or who was clinically dead and revived. ...


The local anesthetic effects are likely from the blocking action of ketamine on sodium channels.[40] Its in vitro blocking potency of sodium channels in the resting state is similar to that of lidocaine[41] Sodium channels are integral membrane proteins that exist in a cells plasma membrane and regulate the flow of sodium (Na+) ions into it. ... Lidocaine (INN) (IPA: ) or lignocaine (former BAN) (IPA: ) is a common local anesthetic and antiarrhythmic drug. ...


Ketamine has a well-documented neuroprotective effect against ischemic brain-injury and glutamate induced brain injury.[42] One hypothesis of its working mechanism in case of chronic pain management and depression is that it works as an anti-dote to an overactivity and in glutamergic brain circuits.


Recreational use

Illicit sale

10 ml bottle of liquid Ketamine drying out into a powder
10 ml bottle of liquid Ketamine drying out into a powder

Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily from veterinary clinics. In the US near its border with Mexico, the drug is most commonly acquired in Mexico, where it can be bought over the counter in veterinary clinics, and smuggled across the border. Image File history File linksMetadata No higher resolution available. ... Image File history File linksMetadata No higher resolution available. ...


In 2006, Operation TKO[citation needed] was a probe conducted by the U.S. Drug Enforcement Agency (DEA). As a result of operation TKO, U.S. and Mexican authorities shut down the Mexico City company, Laboratorios Tokkyo, which was the biggest producer of ketamine in Mexico. According to the DEA, over 80% of ketamine seized in the U.S. is of Mexican origin.[citation needed] The World Health Organization (WHO) Expert Committee on Drug Dependence in its [43] thirty third report] (2003) recommended research into its recreational use/misuse due to growing concerns about its rising popularity in Europe, Asia and North America. Since 1973, the DEA has enforced the drug laws in the United States. ...


Methods of use

Ketamine is sold in either powdered or liquid form. In powdered form, its appearance is similar to that of pharmaceutical grade cocaine and can be insufflated (referred to as a "bump of K"), injected, or placed in beverages. It is also possible to smoke the drug in a joint or pipe, usually mixed with marijuana and tobacco. The smoke has a distinctive bitter taste but the effects of the high hit much faster than when insufflated or ingested. Oral use usually requires more material, but results in a longer trip. However, when administered orally, ketamine is rapidly metabolised to norketamine, which possesses sedating effects; this route of administration is unlikely to produce a dissociative state characteristic of the k-hole. The liquid can be heated to drive off the solvent (usually saline), leaving powder. In therapeutic and psychedelic use, the liquid is typically injected intramuscularly. Intravenous injection is uncommon (recreationally), though possible. It is essentially identical in effect to intramuscular injection, but leads to a much quicker onset — usually within 10 to 15 seconds of dosing. Additionally, intravenous injection tends to lead to a more sudden and marked respiratory depression, especially if the solution is injected at too high of a potency (too fast). These factors make intravenous self-injection dangerous. Ketamine is also commonly combined with other drugs to enhance their effects. More recently in the UK it has been reportedly mixed with cocaine, crushed up 'Ecstasy' tablets - which usually contain one or more stimulant like caffeine and/or amphetamine - MDMA powder. Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ... This article or section does not cite its references or sources. ... In medicine, saline is a solution of sodium chloride (a substance also commonly known as table salt) in sterile water, used frequently for intravenous infusion, rinsing contact lenses, and nasal irrigation (or the yogic practice called jala neti). ... Intramuscular injection is the injection of a substance directly into a muscle. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ...


Psychological effects

Ketamine produces effects similar to PCP and DXM. Like other dissociative anesthetics in low- to upper-middle dosages, its hallucinogenic effects are only seen against a background lacking sensory stimulation, such as darkness. Unlike the other well known dissociatives PCP and DXM, ketamine is very short acting, its hallucinatory effects lasting fifteen minutes or less when insufflated or injected, the total experience lasting no more than one or two hours. “Angel Dust” redirects here. ... Dextromethorphan (DXM or DM) is an antitussive (cough-suppressant) drug found in many over-the-counter cold and cough medicines. ... The general group of pharmacological agents commonly known as hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. ...


Like the other dissociative anaesthetics DXM and PCP, hallucinations caused by ketamine are fundamentally different from those caused by tryptamines and phenethylamines. At low doses, hallucinations are only seen when one is in a dark room with one's eyes closed, while at medium to high doses the effects are far more intense and obvious. These effects include changes in the perception of distances, relative scale, colour and durations/time, as well as a slowing of the visual system's ability to update what the user is seeing. There are reports of high-dosage users being able to see their surroundings in two sharp images, as if the brain is unable to merge the images each eye is sending. Speech often sounds unintelligible i.e. alogia, and auditory hallucinations may occur. At high doses sounds can be out of sync with the user's visual field. Tryptamine (3-(2-aminoethyl)indole) is a monoamine compound that is widespread in nature. ... Phenethylamine, or β-Phenylethylamine, is an alkaloid and monoamine. ... In psychology, alogia, or poverty of speech, is a general lack of additional, unprompted content seen in normal speech. ...


Ketamine produces a dissociative state, characterised by a sense of detachment from one's physical body and the external world. At sufficiently high doses (e.g. 150 mg intramuscular), users may experience what is coined the "K-hole", a state of dissociation whose effects are thought to mimic the phenomenology of schizophrenia. This may include distortions in bodily awareness, such as the feeling that one's body is being tugged, or is gliding on silk, flying, or has grown very large or distended. Users often report feeling more skeletal or becoming more aware of their bones - the shape of their hands is also often of interest. Users may experience worlds or dimensions that are ineffable, all the while being completely unaware of their individual identities or the external world. Users may feel as though their perceptions are located so deep inside the mind that the real world seems distant (hence the use of a "hole" to describe the experience). Some users may not remember this part of the experience after regaining consciousness, in the same way that a person may forget a dream. Owing to the role of the NMDA receptor in long-term potentiation, this may be due to disturbances in memory formation. The "re-integration" process is slow, and the user gradually becomes aware of surroundings. At first, users may not remember their own names, or even know that they are human, or what that means. Movement is extremely difficult, and a user may not be aware that he or she has a body at all.


The best way help someone get out of a "k-hole" quicker, or feel better while they are in thier trip, Is to give them drinks, or foods, that are high in sugar.


Long-term side effects

Main article: Olney's lesions

”In 1989, psychiatry professor John Olney reported that ketamine caused reversible changes in two small areas of the rat brain. 40mg/kg resulted in fluid-filled bags ("vacuoles") appearing inside cells. The bags disappeared after several days, unless high doses of the far more toxic PCP or close relative MK801 were repeatedly given, in which case some cell death was seen. Roland Auer injected monkeys with MK801 and was unable to produce any vacuoles. I asked Auer in 1998 whether persons undergoing anesthesia with Ketalar were at risk of these changes. His reply was that he doubted that it was even a remote possibility because of fundamental differences in metabolism between the rat and human brain. Ketamine can block excito-toxicity (brain damage due to low oxygen, low sugar, epilepsy, trauma etc.) but it can also excite the brain at low doses by switching off the inhibitory system. Why isn't this damaging in monkeys and humans? The answer probably lies in the fact that ketamine binds to an increasingly wide range of different receptors as the dose level rises, and some of these receptors act to shut down the excitement. In humans, by the time a potentially toxic dose is reached, the "excitement window" has been passed and the drug is starting to activate other systems that switch cells off again, a result of ketamine's promiscuity that improves its safety relative to MK801. MK801 binds very specifically to N-P receptors. The other part of the explanation is that rats have rates of brain metabolism that are almost twice as high as those in humans to start with. It is because of this higher base rate of metabolism that ketamine causes over-excitement in rats at doses below those at which it activates shutdown systems.”[44][45][46] Olneys Lesions, also known as NMDA Receptor Antagonist Neurotoxicity (NAN), are a form of brain damage theorized to be caused by high doses of dissociative anaesthetics, particularly those referred to as noncompetitive NMDA-channel-blockers such as ketamine, phencyclidine, and dextromethorphan. ...


Vutskits et al from Geneva showed that short-term exposure of cultures to ketamine at concentrations of > or =20 microg/ml leads to a significant cell loss of differentiated cells and that non-cell death-inducing concentrations of Ketamine (10 microg/ml) can still initiate long-term alterations of dendritic arbor in differentiated neurons, including dendritic retraction and branching point elimination. They also demonstrated that chronic (>24 h) administration of ketamine at concentrations as low as 0.01 microg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks.[47]


Ketamine effects on horses, which where applied by the US army in Arizona during the 1980's proved ketamine provided horses with the faculty to jump notably higher than when they were not under the influence of ketamine.


There is a long list of medicines that could counteract these potential toxic effects, including clonidine, anticholinergics, benzodiazepines and barbiturates.[45][46]


On 21 June 2007 Hong Kong Medical Journal has put up a report regarding the misuse of 'street K'. The report suggests that long term use may result in damage to the liver or urinary bladder, or even acute renal failure. However, the researchers suspect that the damage "may be due to other toxins that the 'street ketamine' has been contaminated with".[48]


In a study of 9 daily ketamine users, Shahani et al found "marked thickening of the bladder wall, a small capacity, and perivesicular stranding, consistent with severe inflammation. At cystoscopy, all patients had severe ulcerative cystitis. Biopsies in 4 patients revealed epithelial denudation and inflammation with a mild eosinophilic infiltrate. Cessation of ketamine use, with the addition of pentosan polysulfate, appeared to provide some symptomatic relief."[49]


Common names

  • K
  • Ketanest
  • Ketaset
  • Ketalar
  • Special K
  • Vitamin K
  • Kitties

References

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See also

The general group of pharmacological agents commonly known as hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. ... An assortment of psychoactive drugs A psychoactive drug or psychotropic substance is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. ...

External links


  Results from FactBites:
 
Ketamine (page 1) (1014 words)
Ketamine causes a rise in intracranial pressure and should not be used in patients who have sustained a recent head injury.
Ketamine crosses the placenta easily and concentrations in the fetus are approximately the same as those in the mother.
Ketamine may be used as the sole anaesthetic agent for a large number of superficial operations and procedures in both adults and children.
ketamine: Definition and Much More from Answers.com (1953 words)
Ketamine is used to manage pain among horses and other large animals, though it has less effect on bovines.
Ketamine may be used in small doses (0.1–0.5 mg/kg/h) as an analgesic, particularly for the treatment of pain associated with movement and neuropathic pain.
Ketamine is also a potent analgesic and can be used in sub-anaesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account.
  More results at FactBites »

 
 

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