the role of differential blockade of alpha-adrenergic agonists in chlorpromazine-induced hypotension.

We studied the effects of chlorpromazine HCl (CPZ) on the pressor responses of norepinephrine and phenylephrine in the isolated, perfused hindlimbs of anesthetized dogs. Our results show that, in contrast to phentolamine, CPZ produced a much greater degree of blockade of the pressor responses of phenylephrine than of norepinephrine. Pre-treatment with cocaine prevented the differential blockade. On the other hand, CPZ acted as a classical competitive antagonist in the isolated femoral artery strip preparation. We conclude that differences in affinity for the Uptake system of the adrenergic nerve endings provide the basis for the differential alpha-adrenergic blocking effect of CPZ. These results explain the finding that although a significant degree of alpha-adrenergic receptor blockade may be present after hypotensive doses of CPZ, responses to the naturally occurring neurotransmitter, norepinephrine, are not decreased.