Taprostene (CG‐4203)

Abstract

The first reports on prostacyclin (PG12), an autocoid released from the vascular endothelium, was published in 1976 (36). Thereafter, major research interest was focused on this interesting substance. The reasons were the unique properties of PG12, being able to relax vascular smooth muscle and to inhibit platelet aggregation at nanomolar concentrations (37). Later on, additional properties of PG12 were discovered, including inhibition of platelet mitogen release (60) and cytoprotective effects (2 1) useful in myocardial ischemia (22). The successful chemical synthesis of PG12 made sufficient quantities of the substance available to allow investigations of its pharmacologic effects in a variety of experimental models and in initial clinical trials.During this early phase of prostacyclin research, its chemical and metabolic instability was recognized as being a major shortcoming in terms of its becoming a clinically important drug (10). The half-life of PG12 at physiologic pH is about 3 min, and chemical stability occurred only at alkaline pH values (i.e., above pH 9). In vivo, the chemical and metabolic instability of the substance led to rapid inactivation by 15-OH-prostaglandin dehydrogenase and other hydrolytic enzymes. Therefore, it became evident very early that only chemically stable PG12 analogs would be useful as clinically relevant drugs (4 1). Chemically stable analogs of PGIz might additionally offer the chance of manipulating some of the pharmacologic properties of the compound to select for certain properties, including platelet inhibition, vasodilation, or inhibition of mitogen release. Additionally, selective chemically stable analogs offer the opportunity of decreasing the incidence of unwanted side effects, which were evident during the first clinical trials with PGIp (i.e., anxiety and headaches).Several chemically stable analogs of PGIz have been synthesized and studied by experimental and clinical pharmacologists. The present review will focus on the pharmacologic properties and clinical effects of taprostene (CG 4203), a compound syn-

In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury.

“…Aggregation studies were performed on cat platelets that were washed as previously described. Platelets were aggregated with 0.1 U/ml of thrombin in the presence or absence of PB1.3 MAg/ml), NBP1.6 (20-40 Mg/ml), or 40 ng/ml of taprostene (i.e., a stable prostacyclin analog) (17). AU aggregation studies were conducted in duplicate, and the results were expressed as a percentage of maximal aggregation (100% light transmittance).…”