Potential use of selective phosphodiesterase inhibitors in the treatment of asthma.
Selective inhibitors of the cyclic nucleotide phosphodiesterase (PDE) isoenzymes have been studied to assess the potential for such agents in the treatment of asthma. A novel selective PDE V inhibitor, SK&F 96231, reversed the bronchoconstriction induced in anaesthetised guinea pigs by histamine, a thromboxane-mimetic or by ovalbumin challenge. There was no effect of SK&F 96231 on heart rate or blood pressure in conscious dogs. Siguazodan (SK&F 94836, a selective PDE III inhibitor) caused bronchodilation but also had cardiovascular effects in conscious dogs. Studies on the PDE profile of various inflammatory cells have indicated that inhibition of PDE IV would be beneficial in the treatment of the inflammatory aspects of asthma and this is briefly reviewed.
Murray
K J
KJ
SmithKline Beecham Pharmaceuticals, Herts, UK.
Eden
R J
RJ
England
P J
PJ
Dolan
J
J
Grimsditch
D C
DC
Stutchbury
C A
CA
Patel
B
B
Reeves
M L
ML
Worby
A
A
Torphy
T J
TJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D011688:Purinones; D011724:Pyridazines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D006146:Guanidines; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D011688:Purinones; D011724:Pyridazines; C073025:2-(2-propoxyphenyl)-6-purinone; C056215:siguazodan; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4