A pharmacological study of two bisbenzylisoquinoline alkaloids, thalistyline and obamegine.
Thalistyline, a monoquaternary bisbenzylisoquinoline alkaloid isolated from Thalictrum sp. inhibited respiration in anesthetized dogs. Thalistyline is about one-fourth as potent as d-tubocurarine in blocking neuromuscular transmission in the rat hemidiaphragm preparation. The pharmacological mechanism of action of the alkaloid is similar to that of d-tubocurarine. Obamegine did not exhibit curare-like activity. On the isolated rabbit aorta, contractions induced by an alpha-adrenoreceptor agonist, phenylephrine, were antagonized by both alkaloids. Increasing concentrations of thalistyline produced parallel shifts to the right in the dose-response curves of phenylephrine. The pA2 value for the competitive pharmacological antagonism was 6.33. Obamegine also antagonized the effects of phenylephrine on the aorta, line and obamegine lowered blood pressure in normotensive dogs. The effect was transient. Repeated injections of the alkaloids resulted in tachyphylaxis to blood pressure lowering effects. Although alkaloids exhibited alpha adrenergic blockade in the vascular preparation, the mechanism for the hypotensive effect remains to be established.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000470:Alkaloids; D011950:Receptors, Cholinergic; D010656:Phenylephrine; C034784:obamegine; C034783:thalistyline