AN INVESTIGATION OF THE ADRENERGIC BLOCKING ACTION OF CHLORPROMAZINE

Abstract

Antagonism by chlorpromazine of the responses of the rabbit aortic strip and the rat seminal vesicle to adrenaline and noradrenaline fulfils the conditions of competitive antagonism. Chlorpromazine was a remarkably potent antagonist (pA₂ approximately 14) of adrenaline and noradrenaline. In the cat anaesthetized with chloralose small doses (1.8 to 4.5 mg/kg) of chlorpromazine greatly reduced or reversed the pressor effect of adrenaline but the pressor effect of noradrenaline was unaffected. A larger dose (9 mg/kg) of chlorpromazine slightly reduced the pressor effect of noradrenaline but caused a spectacular reversal of the pressor effect of adrenaline. This difference was not observed in rabbits and in cats treated with dichloroisoprenaline. Chlorpromazine potentiated the depressor effect of isoprenaline. On the basis of these findings it is concluded that in the cat chlorpromazine in small doses (1.8 to 4.5 mg/kg) has no real adrenergic blocking action and that the selective block of adrenaline pressor effects by these doses is due to a potentiation of adrenergic vasodilatation. Large doses (7.2 to 28.8 mg/kg) of chlorpromazine reduced the pressor effect of noradrenaline; reciprocal analysis showed that this inhibition is competitive.