Examination of medullary α₂ receptors in connection with verapamil induced-hypotension

The interaction of the phenylalkylamine calcium channel blocker, verapamil, at the alpha₂ receptor in the cat brain was studied using radioligand binding and physiological techniques. Specific binding for [³H]yohimbine, a probe for the alpha₂ receptor, was demonstrated in the medulla. The affinity and density of [³H]yohimbine sites were 1.62 Nm and 47 fmol/mg, respectively. Desmethoxyverapamil and the isomers of verapamil were able to displace specific [³H]yohimbine binding. Affinity estimates were 150 Nm for desmethoxyverapamil, 150 Nm for (-)verapamil and 480 Nm for (+)verapamil. We could not detect the presence of [³H]desmethoxyverapamil binding sites in the medulla. To assess the possible physiological role of binding at the alpha₂ receptor in the medulla, verapamil was administered by the intracisternal route in the chloralose/urethane anesthetized cat and the effect on cardiovascular activity was determined. Verapamil (100-1000 nmol) was found to cause hypotension. Pretreatment with yohimbine (100 μg) did not block the verapamil-induced hypotension. The results demonstrate that central administration of verapamil has a hypotensive action. However, this effect does not appear to be due to an interaction at alpha₂ receptors.