THE PHARMACOLOGICAL ACTIONS OF OXYPANAMINE, AN ALKALOID DERIVED FROM THE SEEDS OF ORMOSIA PANAMENSIS

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Department of Health, Education and Welfare, Bethesda 14, Maryland

Oxypanamine is a polycyclic alkaloid of undetermined structure obtained as an air oxidation product of panamine, the latter being a new alkaloid isolated from the seeds of Ormosia panamensis. Oxypanamine is believed to have an N-oxide functional group. In dogs it produces prolonged reduction of systemic blood pressure, elevated pulmonary artery pressure, bronchoconstriction, increased hematocrit, cutaneous erythema and urticaria, effects which ensue following a latent period of 30 to 120 seconds after i.v. injection. Tachyphylaxis to all of these actions is prominent Similar actions were observed in cats, guinea pigs and a chicken but not in rabbits or one monkey. The hypotensive action in dogs is not prevented by atropine or hexamethonium by bilateral section of the vagus and carotid sinus nerves or by spinal cord destruction, nor is it due to adrenergic or ganglionic blockade.

Intra-arterial injections of oxypanamine produce no direct increase in femoral artery blood flow in doses less than those which lower blood pressure when given i.v. Large intra-arterial doses produce a prolonged, delayed increase in flow simultaneously with a fall in systemic arterial pressure. It is concluded that the delayed vasodilatation occurs after the oxypanamine reaches the systemic circulation and is, therefore, an indirect action.

No significant positive or negative cardiac inotropic actions were observed in canine heartlung preparations or in dogs with intact circulatory systems in which cardiac contractile force was measured directly with a strain gauge arch. No efects on the ECG were observed except at the lethal dose, and the changes noted then were attributed to anoxia.

Oxypanamine produces neuromuscular blockade in dogs and chickens similar to the caused by d-tubocurarine. On the basis of a rabbit head-drop assay oxypanamine was found to be about as active as d-tubocurarine. Ganglionic blockade can be demonstrated with very high doses of oxypanamine in dogs and cats maintained under artificial respiration.

Oxypanamine produces other action in dogs such as piloerection, mild sedation, ataxia and potentiation of barbiturate anesthesia. However, no sedation or potentiation of hexobarbital was observed in rats.

A conmparison of the actions of oxypanamine, panamine, N-methylpanamine and the N-oxide of N-methylpanamine has been made. The importance of the presumed N-oxide functional group for both histamine-like and neuromuscular blocking actions is emphasized.