Amir_1985_Biochem.Pharmacol_34_949

Myotubes grown in culture provided a convenient experimental system for the study of the effects of phencyclidine (PCP) and analog drugs on both acetylcholine receptor (AChR) function and on its binding properties. The extent of PCP retention by these cells was studied on the same preparations. PCP, N-ethyl-l-phenylcyclohexylamine (PCE), PCP methiodide (PCPMeI), 1-[1-(3-aminophenyl)-cyclohexyl] piperidine (NH2PCP) and 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP) were found to inhibit carbamylcholine (CbCh)-induced 22Na and 45Ca ion fluxes with 50% inhibition (I50) at 2-6 microM drug concentration. The I50 for CbCh-induced 42K+ efflux was 8-20 microM. Ketamine was less efficient with an I50 of 100 microM. Binding of [125I] alpha-bungarotoxin [( 125I]alpha-BGT) was not affected at drug concentrations that cause 100% inhibition of ion fluxes. Retention of [3H]PCP by the myotubes was a saturable process with half-maximal saturation at approximately 20 microM PCP. It was inhibited by PCP and several tertiary analogs, with and I50 of approximately 20 microM. PCPMeI was much less effective, with an I50 of 1 mM. PCPMeI was, however, as potent as PCP in its inhibition of the AChR function although the amount retained by the cells was 50-fold lower than that of PCP. These results are consistent with the theory that PCP and analog drugs affect AChR at a site other than the alpha-BGT binding site, possibly at the ionic channel of the nicotinic receptor.