The actions of a series of arylpiperazines on rabbit and human corpus cavernosum (CC) smooth muscle were investigated in vitro.Trazodone and its metabolite m-chlorophenylpiperazine (m-CPP) caused a concentration-dependent reduction of noradrenaline (NA)-induced tone in rabbit and human CC by 79±7% and 42±5%, and 74±6% and 31±5%, resp.Trifluoromethylphenylpiperazine (TFMPP) failed to significantly reduce NA-induced tone in CC strips from rabbit (-11±10%) but did reduce tone, at the highest concentration, in human CC strips (-18±5%).The novel arylpiperazine, RSD992, failed to significantly reduce NA-induced tone in CC strips from either species.In rabbit CC subjected to elec. field stimulation (EFS)-induced relaxation, all of the compounds tested caused leftward shifts in the frequency response curve with EF50 values (95% CI) of 10.3 Hz (6.2-14.5 Hz), 9.0 Hz (6.4-11.5 Hz), 6.3 Hz (5.1-7.4 Hz), 2.7 Hz (2.4-2.9 Hz) and 1.8 Hz (1.0-2.5 Hz) for control, RSD992, TFMPP, m-CPP, and trazodone treated CC resp.Enhancement of EFS induced-relaxation was achieved at concentrations of test agents not having significant effects on NA-induced tone or maximal relaxation to 128 Hz stimulation.Based on the above results we suggest that relaxation of CC muscle induced by trazodone, m-CPP and TFMPP may involve enhancement of non-adrenergic non-cholinergic relaxation in addition to direct antagonism of α-adrenoceptors.Furthermore we suggest that the erection enhancing actions of RSD992 in whole animals are not a consequence of direct actions on CC muscle and are therefore less likely to result in priapism.
