PMID: 6405394Mar 1, 1983Paper

The orally active thia-imino-prostacyclin Hoe 892: antiaggregatory and cardiovascular activities

Prostaglandins, Leukotrienes, and Medicine
B A SchölkensW Jung

Abstract

The short chemical half-life limits the potential therapeutic value of Prostacyclin (PGI2). Replacement of the acid-labile enolether structure of PGI2 by a beta-thia-imino group resulted in the orally active and chemically stable analogue Hoe 892. Incubation of rabbit platelet rich plasma with PGI2 and Hoe 892 caused a dose dependent inhibition of collagen and arachidonic acid (AA) induced platelet aggregation with ID50 of 4.2 and 20.1 ng/ml for PGI2 respectively 43.3 and 170.2 ng/ml for Hoe 892. These effects could be potentiated by the phosphodiesterase inhibitor theophylline. Single oral administration of Hoe 892 in conscious rabbits inhibited platelet aggregation for more than 3 hrs with an ID50 of 0.2 mg/kg using collagen and 1.5 mg/kg using AA. These doses were without influence on systemic blood pressure (BP) in conscious rabbits. Intravenous injection of Hoe 892 induced a dose dependent decrease of systemic BP in anesthetized rats (ED25 of 2.2 micrograms/kg) and in the rats with acute renal hypertension. Hoe 892 stimulated renin release in anesthetized rats. The hemodynamic profile in anesthetized dogs (0.5 micrograms/kg/min i.v.) was characterized by a decrease of systemic BP, left ventricular pressure, pulmonary arter...Continue Reading

References

Mar 1, 1977·Prostaglandins·R R GormanO V Miller
Jul 1, 1979·Prostaglandins and Medicine·B A SchölkensU Weithmann
Apr 1, 1979·Prostaglandins·B CooperR I Handin
Jun 1, 1981·Naunyn-Schmiedeberg's Archives of Pharmacology·K SchrörR Ohlendorf
Jan 1, 1980·Angewandte Chemie·W BartmannR H Rupp
May 1, 1981·Prostaglandins·A Dembinska-KiecT Zelazny
Oct 1, 1980·Prostaglandins and Medicine·P G AdaikanL C Lau
Feb 1, 1982·Journal of Medicinal Chemistry·G KovácsG Papp
Jan 1, 1982·British Journal of Pharmacology·M ChiavarelliK M Mullane

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Citations

Apr 1, 1985·Prostaglandins, Leukotrienes, and Medicine·R CeseraniN Mongelli
Dec 1, 1986·British Journal of Pharmacology·T AkibaN Toda
Jan 1, 1985·Medicinal Research Reviews·R C NickolsonH Vorbrüggen

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