Dissociative anaesthetics

Anis, N.A. Berry, S.C. Burton, N.R. and Lodge, D. The dissociative anaesthetics, ketamine and phencyclidine selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Bj J. Pharmacol 79 565-575, 1983. 

Ketamine Another dissociative anaesthetic with similar effects to PCP. 

Phencyclidine A dissociative anaesthetic that causes auditory hallucinations. 

Phencyclidine (PCP) is a synthetic chemical that can be derived from an essential oil of the sassafras tree and is the best-known representative of the class of drugs collectively known as arylcyclohexylamines. As a chemical, PCP was first synthesized in 1926 and was briefly used in the 1950s as a dissociative anaesthetic. The chemicals needed to manufacture PCP are also readily available and inexpensive, and the production process requires little formal chemical knowledge or laboratory equipment. 

Recently, attempts have been made to reconcile the deficiencies in the dopamine hypothesis by focusing on other neurotransmitters that may interact with dopamine in discrete cortical and subcortical neural circuits. In particular, the involvement of the glutamatergic system has received considerable attention. This possibility has arisen from the finding that dissociation anaesthetics such as ketamine and phencyclidine (PCP) can cause a schizophreniform psychosis in normal individuals. Such effects bear a much closer resemblance to the positive and negative symptoms of... 

Phencyclidine (PCP) was first developed as a dissociative anaesthetic in the 1950s, but its use was mainly confined to veterinary anaesthesia after it had... 

Figure 15.7. Structures of the psychotomimetic compound phencyclidine and the structurally related dissociative anaesthetic ketamine.

Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce exdtation of central mammalian neurones by /V-methyl-aspartate. Br J Pharmacol 79(2) 565-575... 

Ketamine, a dissociative anaesthetic, is administered as a racemic mixture (present in the parenteral preparation) and is initially metabolized by the liver to AT-desmethylketamine (metabolite I), which in part is converted by oxidation to the cyclohexene (metabolite II) (Fig. 1.5). The major metabolites found in urine are glucuronide conjugates that are formed subsequent to hydroxylation of the cyclohexanone ring. As the enantiomers differ in anaesthetic potency and the enantioselectively formed (metabolite I has approximately 10% activity of the parent drug) interpretation of the relationship between the anaesthetic effect and disposition of ketamine is complicated. On a pharmacodynamic basis, the S(+) enantiomer is three times as potent as the R(-) enantiomer (Marietta et al., 1977 Deleforge et al., 1991), while the enantiomer that undergoes N-demethylation (hepatic microsomal reaction) differs between species (Delatour et al, 1991). Based on the observed minimum anaesthetic... 

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