Influence of cholinergic modifiers on phencyclidine-induced acute toxicity

Abstract

The effects of pretreatment with mecamylamine (ME), hexamethonium (C-6), d-tubocurarine (DTC), atropine (AT), muscarinic agents 5-methylfurmethide (5-MFT) and O-ethylcholine (EtCh), physostigmine (PH) and cholineacetyltransferase inhibitors 2-benzoyl ethyltrimethylammonium (BETA) and N-naphthylvinylpyridine (NVP) were studied on the lethal action of phencyclidine (PCP) in male Swiss mice. The LD50 of PCP (237 mumol/kg, i.p.) significantly increased by 19% and 10% in ME (14.9 mumol/kg) and PH (0.08 mumol/kg) pretreated groups, respectively. The combined ME and PH pretreatment potentiated the survival of the mice. C-6 (7.3 mumol/kg), DTC (0.11 mumol/kg), AT (14.4 mumol/kg), 5-MFT (1.4 mumol/kg), EtCh (1.7 mumol/kg), BETA (88 mumol/kg) or NVP (74.7 mumol/kg) pretreatment had no significant effect on the LD50 of PCP. However, peripheral parasympathetic effects (defecation, urination, salivation, and lacrimation) of 5-MFT and EtCH in mice were abolished by PCP. Furthermore, low doses of PCP potentiated the peripheral signs in animals pretreated with 5-MFT or EtCh which, however, were abolished by higher doses of PCP. In vivo, administration of PCP was found to have no effect on brain cholinesterase (ChE) activity. These observations have indicated the possibility of central cholinergic mediation during acute toxicity of PCP.