Yangambin: a new naturally-occurring platelet-activating factor receptor antagonist: in vivo pharmacological studies.

The pharmacological profile of a novel specific platelet-activating factor (PAF) receptor antagonist-yangambin-isolated from the Brazilian plant Ocotea duckei Vattimo (Lauraceae), was investigated in the pentobarbitone-anaesthetized rabbit. The i.v. administration of PAF (0.03-3.0 microgram kg-1) induced marked but reversible hypotensive effects and mild reductions in the heart rate. Both effects are independent of the respiratory conditions imposed on the animals. Moreover, PAF (3.0 microgram kg-1, i.v.) induced a reversible decrease of the circulating levels of platelets and of polymorphonuclear leukocytes. Pretreatment with yangambin (10 and 20 mg kg-1, i.v.) dose-dependently attenuated PAF-induced cardiovascular changes and thrombocytopaenia. Nevertheless, the neutropenic leukopaenia elicited by PAF (3.0 microgram kg-1, i.v.) was not prevented by yangambin whereas the reference PAF antagonists WEB 2086 (2 mg kg-1, i.v.) and SR 27417 (1 mg kg-1, i.v.) significantly inhibited the phenomenon. The hypotensive effects of acetylcholine, histamine, and 5-hydroxytryptamine were not affected by prior administration of yangambin. It is concluded that yangambin is a selective antagonist of the cardiovascular effects of PAF which could be useful in pathological states characterized by abnormal PAF release, such as anaphylactic and septic shocks. Furthermore, yangambin might discriminate a PAF receptor subtype present in the cardiovascular system and platelets from the one existing in polymorphonuclear leukocytes in the rabbit.