Furter investigations on the interaction between alpha-adrenoceptor antagonists and the central hypotensive effect of clonidine in rats, rabbits and dogs.

1. The interactions between five alpha-adrenoceptor blocking agents and clonidine have been studied in rats, rabbits and dogs after intracisternal injections. 2. Dibozane, ethomoxane, azapetine, dibenamine and thymoxamine reduced blood pressure in rats and an antagonism of the hypotensive effects of clonidine was detected for the first four drugs. 3. In rabbits, azapetine, dibenamine, dibozane and ethomoxane were hypotensive while thymoxamine had no effect on blood pressure. Dibozane and dibenamine reduced the hypotensive effect of clonidine. 4. In dogs, azapetine, dibozane and ethomoxane reduced blood pressure, while dibenamine induced an increase in blood pressure and thymoxamine was without effect. Only dibenamine antagonized the blood pressure lowering effect of clonidine. A definite conclusion could not be drawn with azapetine due to its long duration of action of action in both rabbits and dogs. 5. These results suggest that the central receptors involved in the hypotensive effect of clonidine differ from many other central receptors and vary according to the animal species. In addition the alpha-adrenoceptor blocking agents appear not to have a unique site and mechanism of action on central cardiovascular control.