title: Effect of a major metabolite of the antiallergic drug repirinast on phosphodiesterase and adenylate cyclase activities.
abstract: MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid, CAS 63768-47-8), a major metabolite of the antiallergic drug repirinast (MY-5116, CAS 73080-51-0), inhibits antigen-induced histamine release from rat peritoneal mast cells. MY-1250 causes a rapid increase in cyclic adenosine monophosphate (AMP) levels in rat peritoneal mast cells. MY-1250 inhibited cyclic AMP phosphodiesterase activities from rat peritoneal cells and guinea pig lung tissue in a concentration dependent manner with IC50 values of 2000 mumol/l and 1670 mumol/l, respectively. However, MY-1250 showed no effect on adenylate cyclase activity from rat peritoneal cells. These results suggest that the inhibitory effect of MY-1250 on histamine release may be partly due to the inhibition of cyclic AMP phosphodiesterase activity.
authors.affiliation: Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: K
authors.initials: K
authors.lastname: Funayama
authors.forename: S
authors.initials: S
authors.lastname: Kadowaki
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Umezu
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D005122:Exudates and Transudates / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006634:Histamine H1 Antagonists; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D005576:Colforsin; C048522:repirinast; C049488:MY 1250; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D004205:Cromolyn Sodium