PHARMACODYNAMIC PROFILE OF PROSTACYCLIN

Since the 1930s and the discovery by von Euler of a vasoactive, lipid- soluble substance that he erroneously assumed was generated by the pro state gland and therefore should be called ''prostaglandin,'' the fami ly of prostaglandins has grown to some 90 substances. These lipid medi ators are derived from arachidonic acid in the ''arachidonic acid casc ade.'' In 1976, while looking for the enzyme that generates the unstab le prostanold thromboxane A(2) from arachidonic acid, Moncada and Vane discovered prostaglandin I-2 and renamed it ''prostacyclin.'' Prostac yclin is the main product of arachidonic acid in all vascular tissues tested to date and strongly vasodilates all vascular beds studied. It is also the most potent endogenous inhibitor of platelet aggregation y et discovered, both inhibiting aggregation and dispersing existing agg regates. It acts through activation of adenylate cyclase, leading to i ncreased levels of cyclic adenosine monophosphate. It also appears to have a ''cytoprotective'' activity, as yet not completely understood. Its effects are short-lasting, disappearing within 30 minutes of cessa tion of infusion. A stable, freeze-dried preparation of prostacyclin ( epoprostenol) is available for administration to humans, and several a nalogs with therapeutically desirable characteristics are currently be ing clinically tested and should become commercially available soon. C linical application of prostacyclin is bedeviled by 2 characteristics: it is pharmacologically unstable, so care must be taken in its use, a nd the correct dosage regimens have not yet been established.