Ss Mbmdkl Shb Kl

Biochemistry and pharmacology

Pharmacodynamics

PCP is well known for its primary action on ionotropic glutamate receptors, such as the NMDA receptor in rats and in rat brain homogenate.[6][7] As such, PCP is an NMDA receptor antagonist. NMDA receptors mediate excitation,[8] however, studies have shown that PCP unexpectedly produces substantial cortical activation in humans[9] and rodents.[10]

Research also indicates that PCP inhibits nicotinic acetylcholine (nACh) receptors. Analogues of PCP exhibit varying potency at nACh receptors[citation needed] and NMDA receptors.[11] In some brain regions, these effects are believed to act synergistically by inhibiting excitatory activity.[citation needed]

PCP, like ketamine, also acts as a D2 receptor partial agonist in rat brain homogenate.[7] This activity may be associated with some of the more psychotic features of PCP intoxication, which is evidenced by the successful use of D2 receptor antagonists (such as haloperidol) in the treatment of PCP psychosis.[12]

Studies on rats indicate that PCP indirectly interacts with endorphin and enkephalin receptors to produce analgesia. [13]

PCP may also work as a dopamine reuptake inhibitor.[14]

Pharmacokinetics

PCP is metabolized into PCHP, PPC and PCAA.

When smoked, some of it is broken down by heat into 1-phenyl-1-cyclohexene (PC) and piperidine.

Conversion of PCP into PC and piperidine by heat. (Image in the PD)

Structural analogues

Possible Analogues of PCP

More than 30 different analogues of PCP were reported as being used on the street during the 1970s and 1980s, mainly in the USA. The best known of these are rolicyclidine (PCPy or 1-(1-phenylcyclohexyl)pyrrolidine); eticyclidine (PCE or N-ethyl-1-phenylcyclohexylamine); and tenocyclidine (TCP or 1-(1-(2-thienyl)cyclohexyl)piperidine). These compounds were never widely used and did not seem to be as well accepted by users as PCP itself, however they were all added onto Schedule I of the Controlled Substance Act because of their putative similar effects.[15][citation needed]

The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP analogues, and summarized below. All of these analogues would have somewhat similar effects to PCP itself, although, with a range of potencies and varying mixtures of anesthetic, dissociative and stimulant effects depending on the particular substituents used. In some countries such as the USA, Australia, and New Zealand, all of these compounds would be considered controlled substance analogues of PCP, and are hence illegal drugs, even though many of them have never been made or tested.[16][17][clarification needed]

Brain effects

Some studies found that, like other NMDA receptor antagonists, phencyclidine can cause a kind of brain damage called Olney's lesions in rats.[18][19] Studies conducted on rats showed that high doses of the NMDA receptor antagonist dizocilpine caused reversible vacuoles to form in certain regions of the rats' brains. All studies of Olney's lesions have only been performed on non-human animals and may not apply to humans.

Phencyclidine has also been shown to cause schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue.[20] It also induces symptoms in humans that mimic schizophrenia.[21]

History and medicinal use

PCP was first synthesized in 1926 and later tested after World War II as a surgical anesthetic. Because of its adverse side effects, such as hallucinations, mania, delirium, and disorientation, it was shelved until the 1950s. In 1953, it was patented by Parke-Davis and named Sernyl (referring to serenity),[22] but was only used in humans for a few years because of side-effects. In 1967, it was given the trade name Sernylan and marketed as a veterinary anesthetic, but was again discontinued[when?]. Its side effects and long half-life in the human body made it unsuitable for medical applications.

Recreational uses

This section needs additional citations for verification. Please help improve this article by adding