Effects of phencyclidine and analog drugs on acetylcholine receptor of cultured muscle cells

Abstract 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-1-phenylcyclohexylamine (PCE), PCP methiodide (PCPMeI), 1-[1-(3-aminophenyl)-cyclohexyl] piperidine (NH 2 PCP) and 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP) were found to inhibit carbamylcholine (CbCh)-induced 22 Na and 45 Ca ion fluxes with 50% inhibition (I 50 ) at 2–6 μM drug concentration. The I 50 for CbCh-induced 42 K + efflux was 8–20 μM. Ketamine was less efficient with an I 50 of 100 μM. Binding of [ 125 I] α-bungarotoxin ([ 125 I]α-BGT) was not affected at drug concentrations that cause 100% inhibition of ion fluxes. Retention of [ 3 H]PCP by the myotubes was a saturable process with half-maximal saturation at ≈20 μM PCP. It was inhibited by PCP and several tertiary analogs, with an I 50 of ≈ 20μM. PCPMeI was much less effective, with an I 50 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 α-BGT binding site, possibly at the ionic channel of the nicotinic receptor.