The cardiovascular and platelet actions of 9β‐methyl carbacyclin (ciprostene), a chemically stable analogue of prostacyclin, in the dog and monkey

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Abstract
9.beta.-Methylcarbacyclin (9.beta.Me; ciprostene) is a synthetic, chemically stable analog of prostacyclin (PGI2; epoprostenol). The platelet anti-aggregating and cardiovascular effects of 9.beta.Me were compared to PGI2 in ansthetized monkeys and dogs. Their hemodynamic effects were compared in open-chest ansthetized dogs and conscious dogs. I.v. infusion of 9.beta.Me and PGI2 to the ansthetized monkey resulted in a dose-dependent hypotension, tachycardia and inhibition of ex vivo ADP-induced platelet aggregation. 9.beta.Me was 72 times less active than PGI2 both as a hypotensive and anti-aggregating agent. I.v. infusion of 9.beta.Me and PGI2 to the anesthetized beagle dog resulted in a qualitatively similar hemodynamic profile. Both substances induced a dose-dependent hypotension accompanied initially by a slightly increased heart rate, a dose-dependent increase in cardiac output, stroke volume and an increased peak LV dP/dt [maximum rate of change in ventricular pressure with time]. At the higher doses studied, the initial increases in the parameters measured were succeeded by dose-dependent falls. 9.beta.Me was 76 x less active than PGI2 as a hypotensive agent. In the anesthetized greyhound, a dose-dependent anti-aggregating and hypotensive effect was seen with either drug, with 9.beta.Me being 23 and 40 x less active than PGI2, respectively. I.v. infusion of 9.beta.Me and PGI2 to the conscious beagle dog induced a dose-dependent hypotension and a variable effect on heart rate. 9.beta.Me was 33 x less active than PGI2 as an hypotensive agent. The duration of the hypotensive response induced by 9.beta.Me was not significantly different from that induced by PGI2 in either monkey or beagle dog.