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Biological effect of orally active platelet-activating factor receptor antagonist SM-10661

Y Komuro, N Imanishi, M Uchida and S Morooka

Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.

SM-10661 [(+/-)-(cis)-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl] displayed marked in vitro inhibition of rabbit platelet aggregation induced by 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkyl-PAF), 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16-PAF), and 1-O- octadecyl-2-acetyl-sn-glycero-3-phosphocholine, with IC50, values of 5.50, 5.94, and 3.68 microM, respectively. It also inhibited alkyl-PAF- induced aggregation of human platelets with an IC50 of 3.00 microM, but it did not inhibit platelet aggregation induced by ADP, collagen, arachidonic acid, the thromboxane A2 agonist U46619, or the Ca ionophore A23187, at concentrations up to 400 microM. Furthermore, SM- 10661 antagonized [3H]-C16-PAF binding to rabbit platelets competitively, with an IC50 of 1.0 microM. SM-10661 protected against alkyl-PAF-induced lethality in mice with an ID50 of 6.0 mg/kg intravenously or 24 mg/kg orally. In guinea pig, SM-10661 inhibited the alkyl-PAF (0.1 micrograms/kg)-induced increase in bronchial pressure, with an ID50 of 0.7 mg/kg intravenously or 15 mg/kg orally. Bronchial hyperreactivity to bombesin after the infusion of alkyl-PAF was also inhibited dose-dependently by the infusion of SM-10661, with an ID50 of 25 mg/kg. In addition, SM-10661 inhibited alkyl-PAF (0.01 micrograms/kg)-induced hypotension in rats, with an ID50 of 0.36 mg/kg intravenously or 33 mg/kg orally. SM-10661, when given orally, showed rapid absorption and good duration of pharmacological activity in rats and rabbits.

Volume 38, Issue 3, pp. 378-384, 09/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


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 J. Pharmacol. Exp. Ther.Home page
D. J. Dupre, C. Le Gouill, M. Rola-Pleszczynski, and J. Stankova
Inverse Agonist Activity of Selected Ligands of Platelet-Activating Factor Receptor
J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 358 - 365.
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