Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors.

1. Low frequency (0.1 Hz) electrical stimulation of the rat isolated vas deferens produced regular contractions that were inhibited by low concentrations of clonidine. 2. The inhibition of the vas deferens produced by clonidine was presynaptic in origin and involved alpha-adrenoceptors. 3. Presynaptic alpha-adrenoceptor antagonist activity was assessed by studying the effects of increasing concentrations of the antagonists on cumulative clonidine dose-response curves on the stimulated vas deferens. 4. Postsynaptic alpha-adrenoceptor antagonist activity was assessed by comparison of control cumulative noradrenaline dose-response curves with those in the presence of increasing concentrations of antagonists in the rat anococcygeus muscle. 5. The results indicate that yohimbine and phentolamine are more potent in blocking presynaptic than postsynaptic alpha-adrenoceptors. Phenoxybenzamine and prazosin block postsynaptic alpha-adrenoceptors preferentially. 6. The findings support the view that presynaptic and postsynaptic alpha-adrenoceptors differ in their sensitivity to alpha-adrenoceptor antagonists.