Reversal of clonidine-induced hypotension by beta-adrenoceptor blocking drugs

The interaction between clonidine, propranolol and sotalol was investigated using conscious normotensive and spontaneously hypertensive rabbits as well as conscious normotensive and spontaneously hypertensive rats. Clonidine (20 micrograms/kg) administration into the marginal ear vein of rabbits produced persistent hypotension and bradycardia. In propranolol (0.5 mg/kg, i.v.)-pretreated animals, clonidine-induced hypotension was prevented. In rats, daily oral or subcutaneous clonidine as well as propranolol produced hypotension and bradycardia. Significant antagonism of the observed hypotensive effects resulted when clonidine was given to propranolol-pretreated animals or when propranolol was added to the treatment regimen of animals being maintained on clonidine. No antagonism between sotalol and clonidine was demonstrable. In view of the known central site of action of clonidine, and the failure of sotalol to antagonize clonidine-induced hypotension it would appear that the central nervous system is a possible site of the observed drug interaction.