15-deoxy-16-hydroxy-16-vinylprostaglandin-e2 and viprostol

CL 115, 129 and its methyl ester, CL 115, 347, were studied for their vasorelaxant effects and compared to that of prostaglandin (PG) E2 and its methyl ester on isolated ductus arteriosus (DA) from fetal lambs and rabbits. CL 115, 129 and CL 115, 347 potently relaxed the oxygen-indomethacin constricted ductus in a concentration dependent manner. The threshold concentration was 1 X 10(-12)M and the estimated EC50's (M) were 6.9 X 10(-8) and 4.3 X 10(-8), respectively, for CL 115, 129 and CL 115, 347. Also confirmed was the vasorelaxant ability of PGE2. These studies indicate that the CL compounds possess potent vasorelaxant effects on the DA although less potent than PGE2 or its methyl ester.

Topics: Animals; Dinoprostone; Dose-Response Relationship, Drug; Ductus Arteriosus; Female; Muscle Relaxation; Pregnancy; Prostaglandins E; Prostaglandins E, Synthetic; Rabbits; Sheep

Topically applied 16-vinylprostaglandins demonstrate the property of rapid transit through the skin and a profound effect on the cutaneous vasculature. At low concentrations in the guinea pig and rabbit. 15-deoxy-16-hydroxy-16-vinyl-PGE2 (DHV-PGE2) and its methyl ester (DHV-PGE2Me) elicit a distinct and persistent erythema which is restricted to the area of application and is not associated with a wheal. Skin temperatures are elevated for several hours following application. Accordingly, these compounds may have therapeutic utility in conditions where local blood flow is compromised or where an enhanced blood flow is desired . In the spontaneously hypertensive rat, topically applied DHV-PGE2 and DHV-PGE2Me produce a dramatic and persistent lowering of blood pressure. The maximal effects are comparable to those obtained wit equal oral or intravenous doses and are maintained for a longer period of time. Moreover, with the topical route, there is no prolongation in the time required for onset of action (3-5 minutes). It appears that while the skin presents only a minimal diffusion barrier to these compounds, a sufficient depot is maintained to give sustained release and prolonged duration. Transdermal delivery of 16-vinyl prostaglandins may offer a convenient means of achieving a clinical antihypertensive effect without the characteristic side effects generally associated with oral or intravascular prostaglandins.

Topics: Administration, Oral; Administration, Topical; Animals; Blood Pressure; Dinoprostone; Epinephrine; Erythema; Guinea Pigs; Injections, Intravenous; Male; Prostaglandins E, Synthetic; Rabbits; Rats; Rats, Inbred Strains; Skin Temperature