The action of chlorpromazine at an isolated cholinergic synapse

The effects of chlorpromazine (CPZ) on cholinergic transmission were studied at the isolated neuromuscular synapse of the frog. It was found that 5 x 10(-6) M CPZ produces the following effects: (1) a reduction in end-plate potential amplitude, mainly through inhibition of transmitter release at presynaptic nerve terminals; (2) a reduction in amplitude of focally recorded end-plate current without detectable change in nerve terminal potential: (3) a decrease in amplitude of miniature end-plate potentials; and (4) an increase in the frequency of spontaneous liberation of transmitter both in normal and calcium-free Ringer's solution. It is concluded that CPZ inhibits cholinergic transmission by a complex action on presynaptic and postsynaptic elements. The relation of these findings to central cholinergic activities of CPZ is discussed.