[Effects of guanfacine on pre- and postsynaptic alpha-adrenoceptors studied in comparison with those of clonidine].
Intravenous injections of guanfacine (1 microgram-3 mg/kg) elevated dose-dependently blood pressure in adrenalectomized, pitched rats. The vasopressor activity of guanfacine was weaker than those of clonidine, an alpha 2-agonist and 1-phenylephrine, an alpha 1-agonist. However, the maximal response produced by guanfacine was the same as that produced by clonidine, while it was much smaller than that produced by 1-phenylephrine. The dose-response curve to guanfacine for increase in blood pressure was shifted in a parallel fashion to the right by 1 mg/kg of yohimbine, an alpha 2-antagonist and by 1 mg/kg of phentolamine, a nonselective alpha 1- and alpha 2-antagonist. However, 0.1 mg/kg of prazosin, a selective alpha 1-antagonist, produced an inhibition of the blood pressure rise induced by higher doses of guanfacine, but not that induced by lower doses. Guanfacine (1 microgram-1 mg/kg) inhibited dose-dependently the tachycardia induced by electrical stimulation of spinal nerves at C7-Th1 in adrenalectomized, pithed rats. The maximal inhibition by guanfacine of heart rate increase induced by electrical stimulation was about 60%. These inhibitory effects were antagonized by yohimbine and phentolamine, but not by prazosin. These results indicate that guanfacine is an alpha 2-agonist with approximately equal potency towards the pre- and postsynaptic alpha 2-adrenoceptors, just as clonidine is, but is weaker as an alpha 2-agonist than clonidine.
D000315:Adrenalectomy; D000316:Adrenergic alpha-Agonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D003655:Decerebrate State; D016316:Guanfacine; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D010648:Phenylacetates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D006146:Guanidines; D010648:Phenylacetates; D015016:Yohimbine; D016316:Guanfacine; D003000:Clonidine; D011224:Prazosin; D010646:Phentolamine