Phencyclidine, oxidation

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... 

Oxidation of cyclic secondary amines such as pyrrolidine (351) and piperidine (353) with iodosobenzene in water leads to lactams 352 and 354, respectively (88TL6913, 88TL6917) (Scheme 90). Similar oxidation of 2-piperidinecarboxylic acid and 2-pyrrolidinecarboxylic acid is accompanied by decarboxylation. Cyclic tertiary amines 355, 357, and 359 (Eq. 48) are likewise oxidized to the corresponding lactams. Other examples include phencyclidine (360) to A-(l-phenylcyclohexyl)piperidone (361), N-(cyanocyclohexyl)piperidine (362) to A-(l-cyanocyclohexyl)piperidone (363) (Scheme 91), and 1,2,3,4-tetrahydroisoquinoline to 1,2,3,4-tetrahy-droisoquinolinone (Eq. 49). 

Bird, D. C., Bujas-Bobanovic, M., Robertson, H. A., Dursun, S. M. Lack of phencyclidine-induced effects in mice with reduced neuronal nitric oxide synthase, Psychopharmacology 2001, 155, 299-309. 

Jewett D. C., Butelman E. R., and Woods J. H. (1996). Nitric oxide synthase inhibitors produce phencyclidine-like behavioral effects in pigeons. Brain Res. 715 25-31. 

Klamer D., Zhang J., Engel J. A., and Svensson L. (2005). Selective interaction of nitric oxide synthase inhibition with phencyclidine behavioural and NMDA receptor binding studies in the rat. Behav. Brain Res. 159 95-103. 

Osawa Y. and Davila J. C. (1993). Phencyclidine, a psychotomimetic agent and drug of abuse, is a suicide inhibitor of brain nitric oxide synthase. Biochem. Biophys. Res. Commun. 194 1435-1439. 

Recent studies suggest all N-methyl-D-aspartate (NMDA) antagonists cause brain damage to the portions of the brain responsible for higher cognitive functions like memory and speech. These are the areas most affected by dissociative anesthetics and include ketamine, dextromethorphan (DXM), phencyclidine (PCP or angel dust), nitrous oxide (whippets), and dizocilpine (MK-801). 

Ketamine belongs to the same family of drugs as dextromethorphan (DXM), which is found in some brands of over-the-counter cough symp nitrous oxide, better known as whippets, so named because of the metal whipped cream chargers the gas is commonly packaged in and phencyclidine (PCP), also known as angel dust. 

Insom-X see GBL GHB Invigorate see GBL GHB Ionamin see Diet pills Iophen DM NR see Dextromethorphan Ischott see Catha edulis Isobutyl nitrite see Inhalants Isocarboxazid Marplan see Antidepressants Isosorbide see Diuretics Iubulu see Catha edulis J La rocha see Rohypnol La salade see Catha edulis LA turnarounds see Dextroamphetamine Lady see Heroin Lady K see Ketamine Laevoamphetamine see Amphetamines Laudanum see Opium Laughing gas see Nitrous oxide LBJ see PCP (phencyclidine) Leaky bolla see PCP (phencyclidine) Leaky leak see PCP (phencyclidine) Lean (codeine cough syrup) see Codeine... 

When-shee see Opium Whip-its see Nitrous oxide Whippets see Nitrous oxide Whippets or whippits see Inhalants White horizon see PCP (phencyclidine)... 

There is speculation that long-term exposure to cyclic tertiary amines such as cocaine, phencyclidine, and phenothiazines may result in biochemical lesions through the formation of reactive metabolites. This premise is supported by the induction of a parkinsonian state by MPTP. Although the initial product of microsomal oxidation is an electrophilic endocyclic iminium intermediate which is thought to be the reactive species primarily responsible for neurotoxicity, there is now evidence that the iminium is in equilibrium with the endocyclic enamine and that the latter is transformed to reactive species. The presence of iminium- detoxifying enzymes in cytosolic and microsomal fractions suggests that rapid inactivation of the iminium... 

Osawa, Y., and Coon, M.J. Selective mechanism-based inactivation of the major phenobarbital-inducible P-450 cMochrome from rabbit liver by phencyclidine and its oxidation product, the iminium compound. DrugMetab Dispos 17(1) 7-13, 1989. 

Figure 7.10. Phencyclidine is oxidized to an iminium species whose role as an intermediate in the inactivation of P450 enzymes is unclear. The structure of cannabidiol (CBD), which also inactivates P450 enzymes by an undefined mechanism, is also shown.

Crowley, J.R. and P.F. Hollenberg (1995). Mechanism-based inactivation of rat liver cytochrome P4502B1 by phencyclidine and its oxidative product, the iminium ion. Drug Metab. Dispos. 23, 786-793. 

Phencyclidine (PCP) was originally developed as an anesthetic for animals, but it has since become an illegal street drug because it is a powerful hallucinogen. Treatment of PCP with excess methyl iodide followed by aqueous silver oxide gives the following three principal products. Draw the structure of PCP. 

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