On the mode of action of chlorpromazine on peripheral adrenergic mechanisms

Abstract

The present study is concerned with the action of chlorpromazine (CPZ) on: the contractile response and the norepinephrine (NE) output following sympathetic stimulation in the isolated perfused spleen of the cat, the intrasplenic removal of infused (arterial inflow) NE in the same preparation, the response of the blood pressure and the cat's nictitating membrane to intravenously and intra-arterially (lingual artery) injected E and NE as well as on the contraction of the nictitating membrane following cervical sympathetic nerve stimulation. The results indicate that chlorpromazine has the following three distinct actions on the peripheral adrenergic neuromuscular junctions: inhibition of uptake of exogenous (injected) and endogenously liberated (sympathetic nerve stimulation) NE into the sympathetic nerve endings; block of α-adrenergic receptors; inhibition of NE liberation from sumpathetic nerve endings by electrical stimulation after higher doses. The inhibition of NE uptake into sympathetic nerve endings (action 1) does not regularly result in a potentiation of the response to exogenous and endogenous NE as is the case with cocaine, since in the spleen and the nictitating membrane, this potentiation is more or less completely compensated or even overcome by the α-adrenergic blocking action (action 2). With higher doses of chlorpromazine the α-adrenergic blocking action predominates, to which inhibition of NE liberation (action 3) by sympathetic nerve activity is added.