Central hypotensive effects of guanfacine in anaesthetised rabbits
Ohkubo, K.; Suzuki, K.; Oguma, M.; Otorii, T.
Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 79(4): 263-274
1982
ISSN/ISBN: 0015-5691 PMID: 7047324 Document Number: 186092
The effects of intracerebroventricular (i.c.v.) injection of guanfacine, a new antihypertensive agent, on blood pressure and heart rate were investigated and compared with those of clonidine in anesthetized rabbits. The i.c.v. injection of guanfacine or clonidine induced a decrease in blood pressure and heart rate in doses which were ineffective by an i.v. route. The depressive effect of guanfacine was less than that of clonidine, but the duration of this action was longer than that of clonidine. A fall in heart rate caused by guanfacine was always less conspicuous than that by clonidine in equipotent hypotensive doses. Decrease in blood pressure and heart rate caused by the 2 drugs were inhibited by i.c.v. pretreatment with phentolamine and 6-hydroxydopamine, respectively. Presynaptic and/or postsynaptic .alpha.-adrenoceptors in the brain may play an important role in the hypotension and bradycardia produced by guanfacine and clonidine. The uptake mechanism at the presynaptic sites of central noradrenergic neurons may be involved in the mode of hypotensive and bradycardia actions of these 2 drugs since these effects were abolished by pretreatment with desipramine, an inhibitor of noradrenaline uptake into the pre-synaptic nerve terminals.