Effects of a contractile prostaglandin antagonist (L-640,035) upon allergen-induced bronchoconstriction in hyperreactive rats and conscious squirrel monkeys.
The effects of an antagonist of contractile prostanoids, L-640,035 (3-hydroxymethyl-dibenzo[b,f]thiepin-5-dioxide) upon antigen-induced bronchoconstriction have been studied in inbred rats with non-specific bronchial hyperreactivity and in conscious squirrel monkeys. L-640,035 was a potent inhibitor of antigen-induced dyspnea (ED50 3.1 mg/kg p.o.) in inbred rats pretreated with methysergide (3 micrograms/kg i.v.) but produced no significant inhibition in untreated rats. Administration of L-640,035 (10 mg/kg p.o.) to conscious squirrel monkeys exposed to aerosols of ascaris antigen markedly inhibited changes in pulmonary resistance (RL) and dynamic compliance (CDYN). At a lower dose (1 mg/kg p.o.) the inhibition of changes in CDYN were similar but the effects on RL were reduced. It was concluded first that contractile prostanoids may be important mediators of antigen-induced bronchoconstriction and secondly that L-640,035 may be effective in human allergic asthma.
D000403:Airway Resistance; D000485:Allergens; D000818:Animals; D000941:Antigens; D001200:Ascaris; D003988:Dibenzothiepins / Q000494:pharmacology*; D004417:Dyspnea / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012129:Respiratory Function Tests; D012453:Saimiri
D000485:Allergens; D000941:Antigens; D003988:Dibenzothiepins; C041107:L 640035