Phencyclidine metabolism

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. 

Six-membered azaheterocycles (i.e.,piperidino derivatives) show a metabolic pattern similar to that of pyrrolidine compounds. Thus, the antiemetic drug diphenidol (5.97, Fig. 5.26) and DN-9893 (5.73) are both metabolized to their co-amino acid and lactam derivatives [177]. In contrast, no lactam metabolite was detected for phencyclidine (5.98, Fig. 5.26), a potent analgesic also widely abused [190]. One may assume that, like for piromidic acid (5.91, Fig. 5.24), steric hindrance at the N-atom is unfavorable for the formation of lactam metabolites. 

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. 

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. 

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. 

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. 

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

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. 

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. 

---