1. The interaction between prazosin and clonidine was studied in anaesthetized rats, pithed rats and in anaesthetized cats.
2. Prazosin diminished the clonidine-induced hypotensive effect in anaesthetized rats, probably via an antagonism at the level of central α-adrenoreceptors.
3. In pithed rats, stimulation of the Nervi accelerantes caused tachycardia, which was diminished considerably by clonidine. The antagonism by clonidine was partly reversed by prazosin, suggesting that prazosin possesses a certain degree of presynaptic activity apart from its predominant effect at the postsynaptic α-receptor. Piperoxan was more active than prazosin.
4. The central hypotensive effect of clonidine, injected into the left vertebral artery of cats was significantly reduced by prazosin, administered before clonidine via the same route. Intravenously injected prazosin did not diminish the central hypotensive effect of clonidine. The antagonism is, therefore, caused by a central mechanism.
5. The combined application of clonidine and prazosin in antihypertensive treatment is probably not only irrational but ought to be discouraged in view of the interaction between the drugs, which leads to a reduced antihypertensive potency of clonidine.