Abstract

A new N-substituted tetrahydroisoquinoline derivative, NC 7197, was investigated for its effects on alpha adrenergic receptors and on the cardiovascular system. The i.v. injection of 0.3 to 10 mg/kg of this compound in anesthetized dogs produced a fall in arterial pressure and increases in cardiac rate and contractile force. After pretreatment with hexamethonium, reserpine or phenoxybenzamine, a presser response to NC 7197 was observed. The positive chronotropic and inotropic effects of NC 7197 were absent in the dog heart-lung preparation; these cardiac effects were also reduced or abolished after beta adrenergic blockade, ganglionic blockade and catecholamine depletion. Acutely denervated, perfused hindlegs of dogs were used to evaluate the effects of the drug on alpha adrenergic receptors. NC 7197, 0.3 to 30 mg/kg, significantly reduced hindleg pressor responses to i.a. norepinephrine, 0.1 to 10 µg. With increasing doses, NC 7197 produced a progressive shift to the right in the dose-response curve for norepinephrine. The duration of blockade was 6 to 10 hours. These results indicate that NC 7197 is a competitive alpha adrenergic blocking agent. Its hypotensive effect appears to be related to the alpha adrenergic blocking activity of the drug on vascular smooth muscle. The data also suggest that the positive chronotropic effect of the drug is the result of a reflex increase in sympathetic tone in response to the decrease in arterial pressure.