Two kinds of modification by 5-methoxy-N,N-dimethyltryptamine of contractile responses to electrical stimulation of isolated guinea-pig vas deferens.

Two kinds of electrical stimulation, low frequency stimulation (5 Hz, 1 msec, 5 pulses, every 20 sec) and high frequency stimulation (30 Hz, 0.1 msec, 20 pulses, every 20 sec), produced contractions in isolated guinea-pig vas deferens. These responses were blocked by alpha, beta-methylene-ATP, but not prazosin. Phentolamine potentiated the contractions produced by low frequency stimulation, while it had little or no effect on the contractions produced by high frequency stimulation. The effect of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a potent short acting hallucinogen, on the contractile response to two kinds of electrical stimulation was examined. On the contraction produced by low frequency stimulation, 5-MeODMT showed a biphasic action. 5-MeODMT at concentrations of 3 X 10(-8)-10(-6) M reduced the contractile response. 5-MeODMT at concentrations of 3 X 10(-6)-2 X 10(-5) M potentiated the contractile response, and this potentiation was reversed by prazosin and ketanserin. Clonidine caused an inhibition of the contractile response to low frequency stimulation. This action of clonidine was reversed by 5-MeODMT. The reverse action of 5-MeODMT was greatly inhibited in the presence of prazosin and ketanserin. The results suggest that 5-MeODMT exerts two different kinds of modification on the contractile response to low frequency stimulation of isolated guinea-pig vas deferens: in one type of modification, 5-MeODMT at concentrations higher than 3 x 10(-8) M exerts an action similar to that of 5-hydroxytryptamine on postganglionic sympathetic nerve terminals and reduces the release of transmitter presynaptically, and in the other type, 5-MeODMT at concentrations higher than 3 x 10(-6) M causes the release of noradrenaline from postganglionic sympathetic nerve terminals.