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European Heart Journal 1992 13(Supplement D):129-135; doi:10.1093/eurheartj/13.suppl_D.129
Copyright © 1992 by the European Society of Cardiology.
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© 1992 The European Society of Cardiology

Pharmacological basis for antihypertensive therapy with a novel dopamine agonist

G. Haeusler, I. Lues, K.-O. Minck, P. Schelling and C. A. Seyfried

Department of Pharmaceutical Research and Development E. Merck, Frankfurter Strasse 250, D-6100 Darmstadt, Germany

Address for correspondence: Dr. Guenther Haeusler, Department of Pharmaceutical Research and Development, E. Merck. Frankfurter Strasse 250, D-6100 Darmstadt, Germany

In the past, nearly all major mechanisms involved in the regulation of blood pressure have become targets of antihypertensive drugs. They include the brain stem with its neuronal circuits of central cardiovascular regulation, the sympathetic neuro-effector system, the kidney, the renin angiotensin aldosterone system and the vascular smooth muscle cell.

There are various ways of influencing the function of the sympathetic nervous system, but the clinical potential of one mechanism of action has not yet been explored in detail. Drugs that inhibit nor adrenaline release through stimulation of inhibitory receptors located at adrenergic nerve terminals in the cardiovascular system (inhibitory presynaptic receptors) are not available for the treatment of hypertension. Among the multiple presynaptic receptors, dopamine receptors which belong to the dopamine2 subtype, are of particular interest.

Carmoxirole is a novel indole derivative with a potent agonist action selective for dopamine2-receptors of the periphery. Experimental evidence shows that carmoxirole lowers blood pressure in various models of hypertension mainly or exclusively through inhibition of noradrenaline release from sympathetic nerve endings. This effect of carmoxirole is mediated by presynaptic dopamine receptors with the characteristic that release inhibition is restricted to low rates of sympathetic nerve discharge.

Key Words: Antihypertensive drugs • carmoxirole • dopamine agonists • dopamine2-receptors • presynaptic dopamine receptors


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