Metabolism of phencyclidine

J. K. Baker, T. L. Little, Metabolism of Phencyclidine. The Role of the Carbinolamine Intermediate in the Formation of Lactam and Amino Acid Metabolites of Nitrogen Heterocycles , J. Med. Chem. 1985, 28, 46-50. 

Laurenzana E, Owens S. Metabolism of phencyclidine by human liver microsomes. Drug Metab Dispos 1997 25 557-563. 

War4 D.P., A.J. Trevor, A. Kalir, J.D. Adams, T.A. Baillie, and N. Castagnoli (1982). Metabolism of phencyclidine. The role of iminium ion formation in covalent binding to rabbit microsomal protein. Drug Metab. Dispos. 10, 690-695. 

The metabolism of the prodines must be assumed to be hydrolysis of the ester, formation of the corresponding piperidinol derivatives, and N-dealkylation, which is the most important step. Possible hydroxylation products analogous to those formed in the metabolism of phencyclidine may also be produced. 

Ward D, Kalir A, Trevor A, Adams J, Baillie T, Castagnoli N. Metabolic formation of iminium species the metabolism of phencyclidine. J Med Chem 1982 25 491-492. 

Shebley M, Jushchyshyn MI, Hollenberg PF (2006) Selective pathways for the metabolism of phencyclidine by cytochrome P450 2B enzymes identification of electrophilic metabolites, glutathione and N-acetyl cysteine adducts. Drug Metab Dispos 34 375-383... 

Fig. 5.26. Metabolism of the piperidine ring according to the mechanism in Fig. 5.23. Diphen-idol (5.97) and DN-9893 (5.73) yield both amino acid and lactam metabolites [177], Phencyclidine (5.98) yields only the amino acid derivative steric hindrance at the N-atom appears to impede formation of the lactam metabolite [190].

In addition, other drugs such as alosetron (2), cyproheptadine (12), diazepam (13) or tamoxifen (49) are AT-demethylated by various microorganisms as a major metabolic route. The carboxylic acid resulting from the oxidative cleavage of the piperidine ring of phencyclidine (36), probably proceeding through an... 

Two recent reviews 22 contain considerable information on the absorption, distribution, metabolism, and excretion of phencyclidine. 

Tonge, S.R., and Leonard, B.E. Partial antagonism of the behavioural and neurochemical effects of phencyclidine by drugs affecting monoamine metabolism. Psychopharmacologla 24 516-520, 1972. 

Chen, Jianping, William Paredes, and Eliot L. Gardner. 1993. "Effects of Acute Phencyclidine on In Vivo Efflux and Metabolism of Dopamine in Nucleus Accumbens, Caudate-Putamen, and Medial Prefrontal Cortex of the Awake, Freely Moving Rat." Einstein Quarterly Journal of Biology and Medicine 10 78-86. 

Khor, S.P., Bozigian, H.andMayersohn, M. (1991) Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling residual tissue blood. 2. Distribution of phencyclidine in the rat. Drug Metabolism and Disposition, 19, 486 190. 

Masumoto, H. Takeuchi, K. Ohta, S. and Hirobe, M. Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine A multi-functional model substrate. Chem Pharm Bull 3Hl) m- 19, 1989. 

Fig. 5.23 a Structure of phencyclidine (PCP). The circled area indicates the site of metabolism leading to the formation of the reactive intermediate b Pathway for for-... 

Meibach, R. C., Glick, S. D., Cox, R., and Maayani, S., 1979, Localisation of phencyclidine-induced changes in brain energy metabolism. Nature (London) 282 625-626. 

Snell, L.D. Mueller, Z.M. Gannon, R.L. Silverman, P.B. and Johnson, K.M. A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine effect i n vitro and dopamine metabolism j n vivo. J. Pharmacol Fxp Ther 231 261-269, 1984. 

Jushchyshyn, M.I., Kent, U.M. and Hollenberg, P.F. (2003) The mechanism-based inactivation of human cytochrome P450 2B6 by phencyclidine. Drug Metabolism and Disposition, 31 (1), 46-52. 

Carroll, F.I., Brine, G.A., Boldt, K.G., Cone, E.J., Yousef-nejad, D., Vaupel, D.B., and Buchwald, W.F. Phencyclidine metabolism Resolution, structure, and biological activity of the isomers of the hydroxy metabolite, 4-phenyl-4-(l-piperidinyl)- cyclohexanol. J. Med. Chem. 24 1047-1051, 1981. 

Dextromethorphan is metabolized by CYP2D6 to dex-trorphan, which binds to phencyclidine receptors and is thought to account for the toxic effects of hallucinations, tachycardia, hypertension, ataxia, and nystagmus. Individuals who are slow metabolizers, those who take long-acting dextromethorphan formulations, and those who take serotonin re-uptake inhibitors or MAO inhibitors are at increased risk of adverse effects. 

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