A new guanidine derivative: dissociation of the adrenergic neuron blocking activity from local anesthetic activity.
Effects of 4-7-exo-methylene-hexahydroisoindoline-ethyl-guanidine hemisulfate (No. 865-123), a new guanidine derivative, on adrenergic neurons and its local anesthetic activity were investigated in comparison with guanethidine. Both derivatives produced in a dose-dependent manner a progressive irreversible reduction of positive chronotropic and contractile responses to postganglionic sympathetic nerve stimulation in isolated rabbit atria. The time course of the reduction by No. 865-123 was somewhat slower. In dogs administered both agents, the pressor response to carotid occlusion was reduced and that to exogenous noradrenaline was potentiated with a slight decrease in blood pressure. Noradrenaline stores in the heart and spleen of rats were also depleted to a similar extent. In the guinea pig weal method, guanethidine acted as a potent local anesthetic with a slow onset and a prolonged action as compared to procaine. No. 865-123 revealed no more anesthetic activity than did saline. It is unlikely that the local anesthetic activity of the guanidine derivatives contributes to the adrenergic neuron blocking activity.
D000779:Anesthetics, Local; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010276:Parasympatholytics; D011817:Rabbits; D051381:Rats; D013154:Spleen / Q000378:metabolism
D000779:Anesthetics, Local; D006146:Guanidines; D010276:Parasympatholytics; C023700:methanohexohydroisoindoline ethylguanidine hemisulfate; D009638:Norepinephrine