Postsynaptic inhibitory effects of phenothiazines at cholinergic synapses may not involve calmodulin.

Treatment of frog cutaneous-pectoris nerve-muscle preparations with calmidazolium (R 24571), a calmodulin-inhibitor, at concentrations of 2 X 10(-7) mol/l and 5 X 10(-7) mol/l had no discernable effect on MEPP amplitude. 10(-6) mol/l calmidazolium caused a small (10-35%) increase in MEPP amplitude in most preparations. The phenothiazine calmodulin-inhibitor chlorpromazine (5 X 10(-6) mol/l) caused a clear reduction in MEPP amplitude (20%) after 30 min treatment. Similar experiments carried out with chlorpromazine sulphoxide (a derivative of chlorpromazine that is 60 X less potent in inhibition of calmodulin-activated enzymes) produced data that were very similar to those obtained with chlorpromazine. It is concluded that the postsynaptic inhibitory effect of phenothiazines at cholinergic synapses is unlikely to involve calmodulin.