The alpha 2-adrenoceptor selectivities and haemodynamic effects of WY26392 and yohimbine in the anaesthetised dog.

The selectivities of WY26392 and yohimbine for prejunctional alpha 2-adrenoceptors have been evaluated in the anaesthetised dog. Clonidine inhibited the tachycardia evoked by cardiac sympathetic nerve stimulation, WY26392 and yohimbine reversed this effect by 50% at doses of 3.3-12 and 7.5-69.5 micrograms/kg respectively, depending upon the frequency of nerve stimulation. The alpha 1-adrenoceptor agonist phenylephrine evoked a pressor response which was reduced by 50% following approximately 1.0 mg/kg of either antagonists. Due to its greater potency at alpha 2-adrenoceptors, WY26392 consistently exhibited a greater selectivity than yohimbine for this receptor. The haemodynamic evaluation of WY26392 and yohimbine revealed that low doses of these compounds (0.03-0.1 mg/kg i.v.) increased systolic blood pressure, heart rate and dp/dtmax. WY26392 evoked a small rise in diastolic blood pressure over this dose range. These increases may be due to an increase in sympathetic nerve activity resulting from alpha 2-adrenoceptor blockade. Higher doses of these compounds reduced these cardiovascular parameters, possibly as a result of alpha 1-adrenoceptor blockade.