In vitro comparison of pre- and postsynaptic effects of dihydroergotoxine mesylate and 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl) piperazine (IP-66).
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.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D004088:Dihydroergotoxine; C040940:IP 66; D011189:Potassium Chloride; D011433:Propranolol; D009638:Norepinephrine