What are the chemical properties of ketamine


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Ketamine is a medicinal substance and is used in human and veterinary medicine to treat pain, to induce anesthesia and, if necessary, to treat asthma. Ketamine takes off by triggering one dissociative anesthesia an exceptional position compared to other analgesics and narcotics, which means the generation of sleep and freedom from pain while largely maintaining the protective reflexes.

As a dissociative, ketamine is also used as a drug.

Clinical information

Ketamine is used in anesthesia for anesthetic purposes and in the treatment of pain (analgesia) in emergency medicine. In contrast to other anesthetics, the circulatory-stable effect is advantageous, which is why ketamine is often used in patients with serious injuries who have unstable circulatory conditions due to blood loss.

Due to the psychotropic side effects, it is usually used in combination with a benzodiazepine such as midazolam, lorazepam or, less often, flunitrazepam.

Due to its bronchodilator properties, ketamine can also be used to treat the therapy-resistant status asthmaticus, although this requires high doses that make endotracheal intubation necessary. However, in most cases of emergency, the ketamine can also be administered alternatively (e.g. intravenous, subcutaneous, intranasal; [with the latter, the necessary blood plasma concentration is not so easy to achieve in the event of a severe attack nasal application may well be a possible as well as practical and acute solution and thus even have a life-saving effect], even if endotracheal intubation is not available - the person should be alone.This enables the patient to help himself or herself as soon as symptoms arise For example, the doctor would have the option of being able to “self-control” - and in addition, through the control of the doctor, albeit to a somewhat lesser extent - to control his medication and thus the symptoms of the disease and to combat them.

Ketamine is also used in veterinary medicine (for example in combination with xylazine in the Hellabrunn mixture) and in pediatrics. Ketamine can be administered nasally, orally, intravenously, and intramuscularly.

The production of a so-called is characteristic of the effect of ketamine dissociative anesthesia. This is understood to mean the generation of sleep and freedom from pain while largely maintaining the reflex activity, in particular the protective reflexes. Ketamine is both a sleep-inducing agent (hypnotic) and a potent analgesic.

According to a study, intravenous administration of ketamine ended depressive episodes in patients with bipolar disorder within 40 minutes. However, the effect was not permanent.[5]

  • Plasma half-life: 2-4 hours; clinical effect significantly shorter because of faster redistribution effect
  • Therapeutic dose: Depending on the objective (analgesia, anesthesia), co-medication and circulatory situation, as well as to be adjusted on a case-by-case basis.

Pharmacological properties

Ketamine was previously available as a racemic mixture of the two enantiomers (S.)- and (R.) -Ketamine available. The general pharmacological profile of (S.) -Ketamine largely corresponds to that of the racemate. The analgesic and anesthetic potency of (S.) -Ketamine is about three times higher than that of the (R.) Form or twice as high as that of the racemate; to achieve similar effects with (S.) -Ketamine compared to the racemate a dose reduction by half is possible. In addition, (S.) -Ketamine is eliminated more quickly and is therefore more controllable overall. In addition to the reduced substance exposure, this clearly leads to shorter wake-up times.[6] The different effects of (R.)- and (S.) -Ketamine has been proven by clinical studies.[7] S-ketamine is available as a medicinal product (also the name of the active ingredient Esketamine) to disposal.

Mechanism of action

The sites and mechanisms of action of the various ketamine effects have only been partially clarified. The most relevant site of action is on the glutamate-NMDA receptor complex. The amino acid glutamic acid (in anionic form as glutamate) is an important neurotransmitter of the central nervous system (CNS), where it causes an influx of calcium that induces a variety of intracellular processes. Ketamine has a non-competitive antagonistic effect on the NMDA receptor using the phencyclidine binding site. Ketamine affects the cholinergic system by preventing the NMDA receptor-dependent acetylcholine release. It also inhibits other glutamate receptors and also shows a weak agonistic effect on opioid receptors. At the GABAA.-Receptor modulates and activates the receptor types α6β2δ and α6β3δ and differs in this from the NMDAR antagonists phencyclidine and dizocilpine.[8] Furthermore, ketamine has an inhibitory effect on the peripheral re-uptake of catecholamines such as norepinephrine and dopamine at the synaptic endplate with intensification of endogenous and exogenous catecholamine effects.

These mechanisms lead to a pronounced stimulation of the cardiovascular system, for example increased heartbeat volume, increased heart rate and increased blood pressure. Overstimulation of the central nervous system or induction of a cataleptic stage causes amnesia. The thalamoneocortical system is dampened and the limbic system is activated. Ketamine acts on the peripheral nervous system both depressively (by blocking the membrane flow) and excitatory (by modifying the sodium channel fraction). It has only minor visceral analgesic effects, but pronounced somatic ones. Furthermore, ketamine seems to have an antidepressant active component that sets in after just two hours.[9]

Side effects and interactions

Very common side effects can be psychotropic effects (pseudohallucinations, unpleasant dreams), nausea and vomiting, increased salivation (hypersalivation), visual disturbances, dizziness and motor restlessness. In addition, ketamine is the only narcotic that increases blood pressure and heart rate; this is desirable for specific indications. In the context of emergency medicine, it is the only drug that can be used to combine circulatory stabilizing and narcotic effects. However, its use in patients with severe coronary heart disease (e.g. heart attack) is to be rejected because the drug increases the work of the heart by increasing the heart rate and blood pressure and thus increases the oxygen consumption of the heart muscle. Ketamine increases eye and intracranial pressure, which is why it should not be used as the only anesthetic in injuries there.[10]

In the event of long-term abuse, ketamine can damage the lower urinary tract. Urological complaints (LUTS) and cystitis with the formation of ulcers (ulcerative cystitis) can occur.[11][12]

In routine anesthesia, ketamine is largely rejected due to its psychotropic side effects. However, the combination with a benzodiazepine can partially prevent the occurrence of nightmares and hallucinations. A stimulus shield is also useful.

Other Information


Calvin L. Stevens, a pharmacologist at Wayne State University (Detroit, Michigan, USA) synthesized as part of a research contract with the Parke-Davis company in search of a substitute for the anesthetic phencyclidine (PCP, "Angel Dust") , the substance ketamine for the first time in April 1962. In 1966 Parke-Davis received a patent[13] for the manufacture of ketamine as a medicinal product for both human and veterinary medicine. Edward Felix Domino, Professor of Clinical Pharmacology at the University of Michigan (USA), carried out his first (non-medical) self-experiment with ketamine on August 3, 1964 and recognized the substance's psychedelic potential. The designation dissociative anesthetic for ketamine he introduced it in 1965.

During the Vietnam War, ketamine was tested on American soldiers and was soon used routinely as an anesthetic in the treatment of combat injuries. In 1970 it was approved as a medicinal product by the Food and Drug Administration. As a street drug, ketamine became widespread from around the mid-1970s.

Legal position

In Germany, Switzerland and Austria, ketamine requires a prescription, but is not subject to the Narcotics Act (Austria: Suchtmittelgesetz).

In the UK, the increased use of ketamine as a drug has led the government to classify the drug as a Class C drug from January 2006.[14] Private property is therefore punishable there and can be punished with up to two years imprisonment, trade with up to 14 years imprisonment. In the meantime, ketamine is also placed under restriction in countries where it was previously freely available (e.g. India).



Ketamine can be produced in a three-step synthesis from 2-chlorobenzonitrile and cyclopentyl magnesium bromide using the Grignard reaction, then reaction with bromine and then with methylamine. Heating in decalin leads to ketamine with ring expansion.


Ketamine stereoisomers:
(R.) Shape (left) and (S.) Shape (right)

Ketamine is a chiral cyclohexanone derivative, related to phencyclidine (PCP) and has a stereocenter. Both the racemate, i. H. the 1: 1 mixture of isomers from (S.) -Ketamine and (R.) Ketamine, as well as the enantiomerically pure eutomer (S.) -Ketamine, also known as esketamine (INN), is used. The (S.) Enantiomer is about twice as effective as the racemic ketamine.

Use as an intoxicant

Due to its dissociative, mind-altering effect, ketamine is also known as a party drug in many European countries (scene names: K, Kate, Barbara, Ket, Kitty, Kiti, Special K, Vitamin K, Multiketamine, Fiction, Keta).[15] The side effects include the ketamine hole and the occurrence of so-called horror trips (nightmare-like scenes with near-death experiences and Tunnel visions).

Ketamine is not only used as a party drug, it is also used in the controversial psycholytic psychotherapy. Hedonistic drug use is also reported, for example in the case of John Cunningham Lilly, where groups of users who are located well outside of any “party scene” undertake “dissociative trips” together.

Cultural reception

  • With the publication of the two books "Journeys Into the Bright World" (Authors: Marcia Moore and Howard Alltounian) and "The Scientist" (John Cunningham Lilly) in 1978, in which the experience with ketamine is described in literary terms, the substance became generally known and then used more and more often as a drug.

Trade names

Ketalar (CH), Ketavet ad us. vet. (D), Ketanest (active ingredient Esketamine, D), numerous generics (D)

Web links

Individual evidence

  1. 1,01,1(RS) -ketamine at ChemIDplus
  2. ^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, pp. 916-917, ISBN 978-0-911910-00-1.
  3. 3,03,13,2data sheet (±) -Ketamine hydrochloride at Sigma-Aldrich, accessed April 7, 2011.
  4. ↑ Since December 1, 2012, only GHS hazardous substance labeling has been permitted for substances. The R-phrases of this substance may still be used to classify preparations until June 1, 2015, after which the EU hazardous substance labeling is of purely historical interest.
  5. ↑ http: //www.aerzteblatt.de/v4/news/news.asp? Id = 42213
  6. ↑ Adams, H.A. & Werner, C. (1997): From racemate to eutomer: (S.) -Ketamine - renaissance of a substance? In: Anesthetist. Vol. 46, pp. 1026-1042. PMID 9451486 doi: 10.1007 / s001010050503
  7. ↑ G. Hempelmann and D. F. M. Kuhn: Clinical significance of S - (+) - ketamine, The anesthesiologist 46 (1997) S3 − S7.
  8. Hevers W, Hadley SH, Lüddens H, Amin J: Ketamine, but not phencyclidine, selectively modulates cerebellar GABA (A) receptors containing alpha6 and delta subunits. In: J. Neurosci.. 28, No. 20, 2008, pp. 5383-93. doi: 10.1523 / JNEUROSCI.5443-07.2008. PMID 18480294.
  9. ↑ Zarate CA Jr et al: A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression. Arch Gen Psychiatry. 2006 Aug; 63 (8): 856-64. PMID 16894061
  10. ↑ Specialist information S-ketanest, As of June 2008
  11. ↑ p. Middela, I. Pearce: Ketamine-induced vesicopathy: a literature review. In: International journal of clinical practice Volume 65, Number 1, January 2011, pp. 27-30, ISSN 1742-1241. doi: 10.1111 / j.1742-1241.2010.02502.x. PMID 21155941.
  12. ↑ R. Hoffman et al .:Ketamine poisoning. UpToDate 19.1, January 2011.
  13. ↑ Patent US3254124.
  14. ↑ BBC News: Club horse ’drug to be outlawed. 28 December 2005
  15. ↑ Frankfurter Allgemeine Sonntagszeitung, April 30, 2006, No. 17 / page 61: Ketamine - party drug from the pharmacy


  • Bolle, Ralf H .: At the origin of longing: depth psychological aspects of changed waking states of consciousness using the example of the anesthetic KETANEST. VWB, Verl. For Wiss. and Education, Berlin 1988, ISBN 3-927408-06-9.
  • Jansen, Karl L. R .: Ketamine: dreams and realities. MAPS, Multidisciplinary Ass. For Psychedelic Studies, Sarasota, Fla. 2001, ISBN 0-9660019-3-1.
  • Lilly, John C .: The scientist. Sphinx-Verlag, 1984 Basel (original title: The scientist: a metaphysical autobiography, translated by Werner Pieper), ISBN 3-85914-413-8.