[Pharmacological effects of [(octahydro-2-azocinyl)methyl] guanidine(guanazodine): its action mechanism and hypotensive effect].
Cardiovascular effects of guanazodine, a new antihypertensive drug, in anesthetized dogs, rabbits and rats and also isolated atria and arteries were compared with those of guanethidine and bethanidine. Guanazodine caused a sustained decrease in the systemic blood pressure of spontaneously hypertensive rats, renal hypertensive dogs and normal cats. No tachyphylaxis developed when the drug was administered orally to the rats once a day for 10 days. The heart rate decreased. Guanazodine relaxed the cat nictitating membrane, attenuated the positive chronotropic response to sympathetic nerve stimulation in anesthetized dogs and in isolated rabbit aorta to transmural electrical stimulation. Guazazodine potentiated the pressor response to noradrenaline but attenuated the response to tyramine in anesthetized cats. The noradrenaline content of rat hearts was significantly reduced 4 hr or later after the injection of guanazodine, while the content in brains and adrenal glands was unaffected. The LD50 of guanazodine injected intravenously to male rats was 136 +/- 11 mg/kg which was approximately 4 times the value of guanethidine and 7 times the value of bethanidine. It may be concluded that the hypotensive effect of guanazodine is related to adrenergic neuron blocking action, the noradrenaline-depleting action in peripheral tissues is similar to the effect of guanethidine and bethanidine, and that the extent and the duration of the hypotension induced by guanazodine are approximately the same as those with guanethidine but appreciably greater than those with bethanidine. Toxicity and side effects appear to be less with guanazodine than with guanethidine and bethanidine.
D000311:Adrenal Glands / Q000032:analysis; D000768:Anesthesia, General; D000818:Animals; D000959:Antihypertensive Agents; D001011:Aorta / Q000187:drug effects; D001627:Bethanidine / Q000494:pharmacology / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000032:analysis; D002415:Cats; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006325:Heart Atria / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D009206:Myocardium / Q000032:analysis; D009541:Nictitating Membrane / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D002395:Catecholamines; D006146:Guanidines; D001627:Bethanidine