Effects of MKS-492 on antigen-induced bronchoconstriction and allergic reaction in guinea pigs and rats.
Effects of R[+]-8-([1-[3,4-dimethoxyphenyl]-2-hydroxyethyl]amino) -3,7-dihydro-7-[2-methoxyethyl]-1,3-dimethyl-1H-purine-2,6-dione (MKS-492), a reported type III isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen- or platelet activating factor (PAF)-induced bronchoconstriction and allergic reactions in guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2) MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in airway responsiveness to histamine in guinea pigs, although aminophylline failed to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle in vitro more potently than aminophylline. 4) MKS-492 inhibited leukotriene B4 (LTB4)-induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently than aminophylline. Both drugs inhibited antigen- and phospholipase A2-induced histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced O2- generation from guinea pig alveolar macrophages. These results indicate that MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or LTB4-induced inflammatory reactions in guinea pigs and the allergic cutaneous reactions in rats when compared to aminophylline.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Sakurai
T
T
Iwama
T
T
Yamaguchi
S
S
Kitagaki
K
K
Inagaki
N
N
Koda
A
A
D000628:Aminophylline / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000941:Antigens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release; D006967:Hypersensitivity / Q000188:drug therapy*; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010972:Platelet Activating Factor / Q000633:toxicity; D011688:Purinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014132:Trachea / Q000187:drug effects
D000941:Antigens; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D011688:Purinones; D013481:Superoxides; C073029:SDZ MKS 492; D007975:Leukotriene B4; D000628:Aminophylline; D006632:Histamine