IP-66

The effect of (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine (IP-66) on the contraction of rat mesenteric artery induced by electric stimulation (ESV) or by injection of norepinephrine (NESV) was compared with the effects of prazosin, yohimbine and dihydroergotoxine mesylate (DHEM). Interference of propranolol on the effects of the 4 alpha-blockers was also considered. Prazosin has proved to be the strongest antagonist of alpha 1-receptors towards which, however, it showed a certain bond latency. In particular conditions related to increased perfusion time and concentrations prazosin also seemed to lose selectivity towards alpha 1-receptors. It was observed that yohimbine is a weak postsynaptic antagonist whereas DHEM showed scarce selectivity. IP-66 proved to be a strong postsynaptic antagonist with negligible presynaptic effect. It was not as strong as prazosin but its bond with alpha 1-receptors appeared more rapid and steady. Results obtained with prazosin or DHEM and propranolol seemed to suggest an equilibrium between beta 2- and alpha 1-receptors shifted towards the latter.

The effects caused on the intestine mesenteric artery preparation by 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl) piperazine (IP-66), a compound having a prevailing alpha-blocking action, and by dihydroergotoxine mesylate (DHEM) were compared in normal conditions and in propranolol-induced beta-receptors block. The two drugs behaved in a completely different way both on vasoconstrictor response (delta p) and on noradrenaline (norepinephrine, NA) outflow induced by electrical stimulation of periarterial nerves. In fact IP-66 inhibited delta p much more than DHEM did but, unlike the latter, it increased NA outflow only at the lowest concentration (8.7 X 10(-9) mol/l) whereas it reduced it at the highest one (2.9 X 10(-7) mol/l). Moreover the effect of IP-6--but not that of DHEM--on NA outflow was completely abolished by propranolol. The hypothesis is put forward that IP-66 may show a strong antagonism towards postsynaptic alpha-receptors and a slight agonism towards presynaptic beta-receptors.