PHENTOLAMINE LACKS ALPHA-2-ADRENOCEPTOR AGONIST ACTIVITY IN ANESTHETIZED DOGS

This study was performed in order to determine whether the blockade of sympathetic vasoconstriction in anaesthetized dogs by phentolamine is due to the antagonist action of the drug at postjunctional adrenoceptors, or is due to depression of neurotransmitter release by an agonist action at prejunctional adrenoceptors. In dogs made areflexic by ganglion blockade with hexamethonium, phentolamine (o.5 mg i.a. or 0.5 mg kg-1 i.v.) elevated or did not affect femoral blood flow. By contrast, clonidine (0.5-2.5 nmol, i.a.) produced femoral vasoconstriction, which was attenuated by prior adminstration of phentolamine. Prior blockade of prejunctional .alpha.2-adrenoceptors with yohimbine (30 .mu.g kg-1, i.v.) did not reduce the blocking the blocking effect of phentolamine (0.5 mg kg-1, i.v.) on neurogenic vasoconstriction. The results indicate that, in anaesthetized dogs, phentolamine lacks appreciable agonist activity at either prejunctional or postjunctional .alpha.2-adrenoceptors. The blockade of neurogenic responses by phentolamine is therefore likely to due to postjunctional adrenoceptor blockade.