Correlation between in vitro cyclic adenosine monophosphate phosphodiesterase inhibition and in vivo anti-inflammatory effect.
We tested the hypothesis that topical adenosine monophosphate phosphodiesterase (cAMP PDE) inhibitors are anti-inflammatory. These can be shown by a correlation between PDE inhibitory and anti-inflammatory function of a series of known PDE inhibitors. The effect of various cAMP PDE inhibitors on PDEs isolated from HaCaT cells was first investigated. These compounds were then tested as anti-irritants against topical 8% Balsam of Peru. A direct correlation was observed between the in vitro EC(50) values for PDE inhibition and the in vivo anti-inflammatory potential with a correlation coefficient of r = 0.79. These results stress the value of PDE inhibitors as anti-inflammatory agents in topical use, and also demonstrate that the in vitro PDE assay can be used to predict in vivo anti-inflammatory potential.
Goyarts
E
E
Estee Lauder, Melville, NY, USA.
Mammone
T
T
Muizzuddin
N
N
Marenus
K
K
Maes
D
D
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001453:Balsams / Q000633:toxicity; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007509:Irritants / Q000037:antagonists & inhibitors / Q000633:toxicity; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000201:enzymology*
D000893:Anti-Inflammatory Agents; D001453:Balsams; D004791:Enzyme Inhibitors; D007509:Irritants; C025080:Peruvian balsam; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases