Abstract
Intravenous injections of guanfacine (1 μg-3 mg/kg) elevated dose-dependently blood pressure in adrenalectomized, pithed rats. The vasopressor activity of guanfacine was weaker than those of clonidine, an α2-agonist and 1-phenylephrine, an α1-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 doseresponse curve to guanfacine for increase in blood pressure was shifted in a parallel fashion to the right by I mg/kg of yohimbine, an α2-antagonist and by 1 mg/kg of phentolamine, a nonselective α1- and α2-antagonist. However, 0.1 mg/kg of prazosin, a selective α1-antagonist, produced an inhibition of the blood pressure rise induced by higher doses of guanfacine, but not that induced by lower doses. Guanfacine (1 μg-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 α2-agonist with approximately equal potency towards the pre- and postsynaptic α2-adrenoceptors, just as clonidine is, but is weaker as an α2-agonist than clonidine.
