[Effects of a cyclic nucleotide phosphodiesterase isoenzyme type III inhibitor, SDZ MKS 492 on airway responsiveness in beagles].
To elucidate the effects of cyclic nucleotide phosphodiesterase (PDE) isoenzyme inhibition on airway responsiveness, we studied the effects of a selective PDE isoenzyme type III inhibitor, SDZ MKS 492, on airway responsiveness to inhaled methacholine (Mch) in 6 beagles. Base-line respiratory resistance and airway responsiveness to Mch were determined by modified Astograph (7 Hz oscillation method). SDZ MKS 492 (1.0 mg/kg, 0.3 mg/kg or 0.1 mg/kg) was orally administered 1 hr prior to the determination of airway responsiveness at intervals of one week. Base-line respiratory resistance was decreased in a dose-dependent manner by SDZ MKS 492. SDZ MKS 492 significantly decreased airway responsiveness to Mch (log D min) in a dose-dependent manner, and the airway responsiveness (log PD2.0 Mch) was significantly decreased by 1.0 mg/kg of SDZ MKS 492. These results indicate that selective inhibition of PDE isoenzyme type III results in a decrease in respiratory resistance and airway responsiveness.
Imai
T
T
First Department of Internal Medicine, School of Medicine, Showa University.
Adachi
M
M
Idaira
K
K
Horikoshi
S
S
Sugeta
A
A
Takahashi
T
T
Tanaka
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology*
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; C073029:SDZ MKS 492; D015105:3',5'-Cyclic-AMP Phosphodiesterases