Ketamine pharmacological effects

Both phencyclidine and ketamine bind with high affinity to a number of receptors in the brain, but it is now accepted that the primary target is the sigma-PCP receptor site located in the ion channel of the NMDA excitatory amino acid receptor complex. The precise function of this receptor in the brain is still the subject of debate. It is now known that there are two distinct sigma receptor sites in the mammalian brain (ctj and a2) which are not associated with the NMDA receptor complex. Haloperidol and the atypical neuroleptic remoxipride bind with high affinity to such sites, and it has been postulated that some typical and atypical neuroleptics may owe some of their pharmacological effects to their action on such receptors. 

Ketamine, more commonly known on the street as Special K and to the scientist as ketamine hydrochloride, is a unique drug with a combination of pharmacological effects. Although it is primarily used by veterinarians as an animal tranquilizer, it is available for limited uses in humans. Chemically, it is similar to phencyclidine (PCP or angel dust), a Schedule II drug that was the first of a new class of general anesthetics called dissociative anesthetics. As the name implies, dissociative anesthetics produce in patients a feeling of detachment and disconnection from pain and the environment. 

The pharmacological effects of the R- and 5-enantiomers of ketamine have been compared in 11 subjects who received //-ketamine 0.5 mg and then 5-ketamine 0.15 mg, separated by 1 week (432). Before and after each drug administration they were subjected to a painful stimulus using a nerve stimulator applied to the right central incisor tooth. Pain suppression was equal with the two drugs. The subjects reported more unpleasant psychotomimetic effects with 5-ketamine and more pleasant effects with //-ketamine. Seven of eleven subjects preferred //-ketamine, while none preferred 5-ketamine. These results suggest that the neuropsychiatric effect of ketamine may be predominantly due to the 5-enantiomer, and that //-ketamine may be a better alternative. This study is in direct distinction to earlier work suggesting that //-ketamine is responsible for most of the undesirable neuropsychiatric side effects of ketamine. 

The pharmacological effects of tiletamine plus zolazepam are very similar to the effects produced by ketamine. When used as the sole anesthetic in the horse, tiletamine plus zolazepam can cause excitation and hyperresponsiveness. This combination is only used in the horse after adequate sedation. In general, it produces a dose-related loss of consciousness, characterized as a cataleptic state, and analgesia. Ocular and airway reflexes are well maintained. The combination induces mild cardiovascular stimulation secondary to centrally mediated sympathetic nervous system stimulation. There is minimal respiratory depression. 

W G Cohen ML and Trevor AJ, Cerebral accumulation of ketamine and the relation between metabolism of the drug and its pharmacological effects, fPET, 189, 351-358 (1974). 

General pharmacologic effects ketamine is an anesthetic agent which produces a... 

Although generally similar pharmacologic profiles were obtained for the phencyclinoids, subtle but perhaps important differences in these compounds were discernible depending upon the individual assay employed. For example, ketamine never produced behavioral convulsions and was least potent with respect to SLA and disruption of rotarod performance, but was more potent than PCPY, TCPY, TCP, and PCA in the assessment of analgesic activity. PCA, which was very effective in decreasing the severity of electroshock convulsions, was not particularly efficacious or potent in other assays. While PCE was equipotent with PCP in stimulating SLA, it was least efficacious of all compounds with respect to peak SLA achieved. 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

Ketamine and also tiletamine are structurally and pharmacologically related to phencyclidine. Its mechanism of action is not well understood. It has been suggested that it blocks the membrane effects of the excitatory neurotransmitter glutamic acid. Ketamine produces dissociative anesthesia, which means that the patient seems to be awake but there are no responses to sensory stimuli. Ketamine, which can be administered IV or IM, has strong analgesic activity. It is especially indicated for interventions of short duration without any need for skeletal... 

Ketamine, a weakly basic compound structurally and pharmacologically similar to phencyclidine, is utilized in the U.S. to induce anesthesia.1 It is available in solution for intravenous or intramuscular injection. Since the drug is pharmacologically similar to PCP it has the potential of producing hallucinogenic effects and, therefore, in recent years has become a drug of abuse. 

The pharmacology of ketamine, including its adverse effects, has been reviewed (4), as has the use and adverse effects of 5-ketamine in the intensive care unit (5). 

Artru A A 1990 Hypocapnia and diazepam reverse and midazolam or fentanyl attenuates ketamine induced Increase of cerebral blood volume and/or cerebrospinal fluid pressure. In Domino E F (ed) Status of ketamine in anesthesiology. NPP Books, Ann Arbor, Ml, p. 119 Aurich C, Aurich J E, Klug E 1993 Naloxone affects gastrointestinal functions and behaviour in horses. Deutsche Tierarztiiche Wochenschrift 100 314-315 Ballard S, Shults T, Kownacki A A et al 1982 The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse. 

Cardiopulmonary effects of ephedrine in halothane-anesthetized horses. Journal of Veterinary Pharmacology and Therapeutics 12 389-396 Greene S A, Thurmon J C, Tranquilli W J et al 1986 Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies. American Journal of Veterinary Research 47 2364-2367... 

Sams R, Pizzo P 1987 Detection and identification of ketamine and its metabolites in horse urine. Journal of Analytical Toxicology 11 58-62 Sarazan R D, Starke W A, Krause G F et al 1989 Cardiovascular effects of detomidine, a new U2-adrenoceptor agonist, in the conscious pony. Journal of Veterinary Pharmacology and Therapeutics 12 378-388... 

Waterman, A.E. (1984) The pharmacokinetics of ketamine administered intravenously in calves and the modifying effect of premedication with xylazine hydrochloride. Journal of Veterinary Pharmacology and Therapeutics, 7, 125-130. 

Deleforge, J., Davot, J.L., Boisrame, B. Delatour, P. (1991) Enantioselectivity in the anaesthetic effect of ketamine in dogs. Journal of Veterinary Pharmacology and Therapeutics, 14, 418-420. 

Much of the basic pharmacology of glutamate receptors was elucidated from these two spinal cord preparations in vivo or in vitro. Thus, the differential sensitivity of neurones to kainate, quisqualate and NMDA [3], the differential antagonistic effects of DAA, HA-966, GAMS, GDEE, D-AP5, Mg + and ketamine [6-9, 19] and the effects of these antagonists on S3maptic transmision [11-13, 95] were initially described in these spinal preparations. 

Phencyclidine (PCP) and the related compound ketamine have a mixture of clinical effects that reflects their complex pharmacology. Although acting on a specific subset of serotonin-type (HT-2) receptors in the forebrain,22 PCP also has affinity for cholinergic, opiate, and dopamine receptors. This may explain PCP s ability to produce subjec-... 

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