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Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine
Author(s) -
Motasim Billah M.,
Egan Robert W.,
Ganguly Ashit K.,
Green Michael J.,
Kreutner William,
Piwinski John J.,
Siegel Marvin I.,
Villani Frank J.,
Wong Jesse K.
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536525
Subject(s) - histamine , antagonist , platelet activating factor , pharmacology , chemistry , in vivo , bronchospasm , guinea pig , in vitro , stereochemistry , medicine , biochemistry , endocrinology , asthma , receptor , biology , microbiology and biotechnology
From a series of amide analogs of the histamine H 1 antagonist, azatadine, a potent, orally active, dual platelet‐activating factor (PAF) and histamine antagonist, Sch 37370, namely 1‐acetyl‐4‐(8‐chloro‐5,6‐dihydro‐11 H ‐benzo‐[5,6]cyclohepta[1,2‐b]pyridin‐11‐ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF‐induced aggregation of human platelets in vitro (IC 50 =0.6 μM), and in vivo inhibits PAF‐ and histamine‐induced bronchospasm in guinea pigs with ED 50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.