Abstract
A variety of drugs were screened to determine which were capable of blocking the behavioral stimulation produced in mice by acute administration of phencyclidine (PCP). Chlorpromazine and clozapine blocked PCP-induced stimulation, while haloperidol, reserpine, and alpha-methyl-p-tyrosine did not. The GABA receptor agonists imidazole acetic acid and muscimol blocked PCP, but other drugs that influence GABA, such as dipropylacetic acid, baclofen, and diazepam, were ineffective. Yohimbine and methysergide also blocked PCP in high dosages, but other drugs with comparable alpha-noradrenergic and serotonergic blocking properties (phentolamine, cyproheptadine, and cinnanserin) were ineffective. Cholinergic and anticholinergic drugs, beta-noradrenergic and opiate antagonists, and nonspecific sedatives and convulsants were also ineffective. These finding suggest that chlorpromazine, clozapine, yohimbine, and methysergide may share a property that is unlike their primary known modes of action on dopaminergic, alphanoradrenergic, and serotonergic neurotransmitter systems, and that this property accounts for their ability to block PCP. However, the effectiveness of GABA agonists appears to be mediated through direct activation of GABA receptors. It is suggested that chlorpromazine and imidazole acetic acid should be considered as possible drug treatments for PCP toxicity.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Allen RM, Young SJ (1978) Phencyclidine-induced psychosis. Am J Psychiatry 135:1081–1084
Burns RS, Lerner SE (1976) Perspectives: Acutes phencyclidine intoxication. Clin Toxicol 9:477–501
Chen G, Ensor, CR, Russell D, Bohner B (1959) The pharmacology of l-(l-phenylcyclohexyl) piperidine HCl. J Pharmacol Exp Ther 127:241–250
Costa E, Greengard P (1975) Mechanism of action of benzodiazepines. Raven Press, New York
Domino EF (1978) Neurobiology of phencyclidine — An update. In: Petersen RC, Stillman RC (eds) PCP-Phencyclidine abuse: An appraisal. National Institute of Drug Abuse Monograph Research Series 21, p 18
Enna SJ, Snyder SH (1977) Influences of ions, enzymes, and detergents on γ-aminobutyric binding to synaptic membranes of rat brain. Mol Pharmacol 13:442–453
Finnegan KT, Kanner MI, Meltzer HY (1976) Phencyclidine-induced rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents. Pharmacol Biochem Behav 5:651–660
Garey RE, Health RG (1976) The effects of phencyclidine on the uptake of 3H-catecholamines by rat striatal and hypothalamic synaptosomes. Life Sci 18:1105–1110
Haas HL, Anderson EG, Hosli L (1973) Histamine and metabolites: Their effects and interactions with convulsants on brain stem neurons. Brain Res 51:269–278
Johnson KM (1978) Neurochemical pharmacology of phencyclidine. In: Petersen RC, Stillman RC (eds) PCP-Phencyclidine abuse: An appraisal. National Institute on Drug Abuse Monograph Research Series 21, p 44
Kanner M, Meltzer HY, Davis JM (1975) Pharmacologic aspects of the locomotor stimulation produced by phencyclidine in the rat. Neurosci Abstracts 1:237
Kloog Y, Gabrialevitz A, Kalir A, Balderman D, Sokolovsky M (1979) Functional evidence for a second binding site of nicotinic antagonists using phencyclidine derivatives. Biochem Pharmacol 28:1447–1450
Leonard BE, Tonge SR (1970) Some effects of a hallucinogenic drug (phencyclidine) on neurohumoral substances. Life Sci 9: (1):1141–1152
Luisada PV (1978) The phencyclidine psychosis: Phenomenology and treatment. In: Petersen RC, Stillman RC(eds) PCP-Phencyclidine abuse: An appraisal. National Institute on Drug Abuse Monograph Research Series 21, p 241
Luisada PV, Brown BI (1976) Clinical management of the phencyclidine psychosis. Clin Toxicol 9:539–545
Liden CB, Lovejoy FH, Costello CF (1975) Phencyclidine: Nine cases of poisoning. JAMA 234:513–516
Maayani S, Weinstein H, Ben-Zvi N, Cohen S, Sokolovsky M (1974) Psychotomimetics as anticholinergic agents — I: 1-cyclohexypiperidine derivative: Anticholinesterase activity and antagonistic activity to acetylcholine. Biochemical Pharmacology 23: 1263–1281
Martin JR, Berman MH, Krewsun I, Small SF (1979) Phencyclidine-induced stereotyped behavior and serotonergic syndrome in the rat. Life Sciences 24:1699–1704
Meltzer HY, Fessler RG, Simonovic M, Sturgeon D (1979) Letter. Am J Psychiatry 136:235
Menon MK (1979) Letter. Am J Psychiatry 136:236–237
Misra AL, Pontani RB, Bartolomea J (1979) Persistance of phencyclidine (PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioral effects. Res Commun Chem Pathol Pharmacol 24:431–435
Mohler H, Okada T, Enna SJ (1978) Benzodiasepine and neurotransmitter receptor binding in rat brain after chronic administration of diazepam or phenobartital. Brain Res 156:391–395
Murray TF, Horita A (1979) Phencyclidine-induced stereotyped behavior in rats: Dose-response effects and antagonism by neuroleptics. Life Sci 24:2217–2226
Naik SR, Guidotti A, Costa E (1976) Central GABA receptor agonists: Comparison of muscimol and baclofen. Neuropharmacology 15:479–484
Paster Z, Maayani S, Weinstein H, Sokolovsky M (1974) Cholinolytic action of phencyclidine derivatives. Eur J Pharmacol 25:270–274
Rainey JM, Crowder MK (1975) Prolonged psychosis attributed to phencyclidine: Report of three cases. Am J Psychiatry 132:1076–1078
Saito K, Konishi S, Otsuka M (1975) Antagonism between lioresal and substance P in rat spinal cord. Brain Res 97:177–180
Schlemmer RF, Jackson JA, Preston KL, Bederka JP, Garver DL, Davis JM (1978) Phencyclidine-induced stereotyped behavior in monkeys: Antagonism by pimozide. Eur J Pharmacol 52:379–384
Shoulson I, Goldblatt D, Charlton M, Joynt RJ (1978) Huntington's disease: Treatment with muscimol, a GABA-Mimetic drug. Ann Neurol 4:279–284
Showalter CV, Thornton WE (1977) Clinical pharmacology of phencyclidine toxicity. Am J Psychiatry 134:1234–1238
Simler S, Ciesielski L, Maitre M, Randrianarisoa H, Mandel P (1973) Effect of sodium n-dipropylacetate on audiogenic seizures and brain γ-aminobutyric acid level. Biochem Pharmacol 22:1701–1708
Smith RC, Meltzer HY, Arora RC, Davis JM (1977) Effects of phencyclidine on (3H)catecholamine and (3H)serotonin uptake in synaptosomal preparations from rat brain. Biochem Pharmacol 26:1435–1439
Tamminga CA, Crayton JM, Chase TN (1978) Muscimol: GABA agonist therapy in schizophrenia. Am J Psychiatry 135:746–747
Vincent JP, Cavey D, Kamenka JM, Geneste P, Lazdunski M (1978) Interaction of phencyclidines with the muscarinic and opiate receptors in the central nervous system. Brain Res 152:176–182
Wyatt RJ (1976) Biochemistry and schizophrenia (Part IV). The neuroleptics — their mechanism of action: A review of the biochemical literature. Psychopharmacol Bull 12:5–50
Yesavage J, Freeman AM (1978) Acute phencyclidine (PCP) intoxication: Psychopathology and prognosis. J Clin Psychiatry 44:664–665
Yesavage J, Freeman AM (1979) Letter. Am J Psychiatry 136:235–236
Yorkston NJ, Zaki SA, Malik MKU, Morrison RC, Havard CWH (1974) Propranolol in the control of schizophrenic symptoms. Brit Med J iv:633–635
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Freed, W.J., Weinberger, D.R., Bing, L.A. et al. Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice. Psychopharmacology 71, 291–297 (1980). https://doi.org/10.1007/BF00433064
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00433064