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Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor.
J Pharmacol Exp Ther. 1987 Jun; 241(3):974-81.JP

Abstract

WEB 2086, a thieno-triazolodiazepine, is a potent and specific antagonist of platelet activating factor (PAF) in vitro and in vivo. This compound inhibits PAF-induced human platelet and neutrophil aggregation in vitro (IC50 = 0.17 and 0.36 microM, respectively) but has little or no effect on the action of other platelet aggregating agents. In comparison with kadsurenone, ketotifen or thiazinamium chloride, WEB 2086 was 26 to 200 times more potent in the PAF-induced platelet aggregation. In anesthetized guinea pigs, pretreatment with 0.1 to 2.0 mg/kg p.o. or 0.01 to 0.5 mg/kg i.v. of WEB 2086 inhibits dose-dependently the accumulation and aggregation of 111Indium labeled platelets, bronchoconstriction, systemic hypotension and also the lethal effect due to an i.v. PAF infusion [30 ng/(kg X min)] or intratracheal instillation of PAF (300 micrograms/kg). Under the same experimental conditions in guinea pigs, WEB 2086 given by inhalation achieved a similar anti-PAF activity. In anesthetized rats, the hypotension induced by an i.v. PAF infusion was also reversed (ED50 = 0.052 mg/kg i.v.). The increase in cutaneous vascular permeability due to intradermal PAF (25 ng/site) was inhibited dose-dependently by WEB 2086 (0.025-2 micrograms/site) in rats. Because of its structural relationship to triazolodiazepines, WEB 2086 was examined for anticonvulsant and sedative action. Up to doses of 300 and 800 mg/kg p.o., respectively, no effects were found. In conclusion, WEB 2086 is a potent and specific PAF antagonist with triazolodiazepine structure but without sedative activity.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

3598913

Citation

Casals-Stenzel, J, et al. "Pharmacological Actions of WEB 2086, a New Specific Antagonist of Platelet Activating Factor." The Journal of Pharmacology and Experimental Therapeutics, vol. 241, no. 3, 1987, pp. 974-81.
Casals-Stenzel J, Muacevic G, Weber KH. Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. J Pharmacol Exp Ther. 1987;241(3):974-81.
Casals-Stenzel, J., Muacevic, G., & Weber, K. H. (1987). Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. The Journal of Pharmacology and Experimental Therapeutics, 241(3), 974-81.
Casals-Stenzel J, Muacevic G, Weber KH. Pharmacological Actions of WEB 2086, a New Specific Antagonist of Platelet Activating Factor. J Pharmacol Exp Ther. 1987;241(3):974-81. PubMed PMID: 3598913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. AU - Casals-Stenzel,J, AU - Muacevic,G, AU - Weber,K H, PY - 1987/6/1/pubmed PY - 1987/6/1/medline PY - 1987/6/1/entrez SP - 974 EP - 81 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 241 IS - 3 N2 - WEB 2086, a thieno-triazolodiazepine, is a potent and specific antagonist of platelet activating factor (PAF) in vitro and in vivo. This compound inhibits PAF-induced human platelet and neutrophil aggregation in vitro (IC50 = 0.17 and 0.36 microM, respectively) but has little or no effect on the action of other platelet aggregating agents. In comparison with kadsurenone, ketotifen or thiazinamium chloride, WEB 2086 was 26 to 200 times more potent in the PAF-induced platelet aggregation. In anesthetized guinea pigs, pretreatment with 0.1 to 2.0 mg/kg p.o. or 0.01 to 0.5 mg/kg i.v. of WEB 2086 inhibits dose-dependently the accumulation and aggregation of 111Indium labeled platelets, bronchoconstriction, systemic hypotension and also the lethal effect due to an i.v. PAF infusion [30 ng/(kg X min)] or intratracheal instillation of PAF (300 micrograms/kg). Under the same experimental conditions in guinea pigs, WEB 2086 given by inhalation achieved a similar anti-PAF activity. In anesthetized rats, the hypotension induced by an i.v. PAF infusion was also reversed (ED50 = 0.052 mg/kg i.v.). The increase in cutaneous vascular permeability due to intradermal PAF (25 ng/site) was inhibited dose-dependently by WEB 2086 (0.025-2 micrograms/site) in rats. Because of its structural relationship to triazolodiazepines, WEB 2086 was examined for anticonvulsant and sedative action. Up to doses of 300 and 800 mg/kg p.o., respectively, no effects were found. In conclusion, WEB 2086 is a potent and specific PAF antagonist with triazolodiazepine structure but without sedative activity. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/3598913/Pharmacological_actions_of_WEB_2086_a_new_specific_antagonist_of_platelet_activating_factor_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=3598913 DB - PRIME DP - Unbound Medicine ER -