The antiinflammatory activity of topically applied novel calcium-channel antagonists.
The antiinflammatory activities of two novel calcium-channel antagonists, AGN 190742 and AGN 190744, were evaluated in murine models of cutaneous inflammation. These 2(5H)-furanone ring compounds block both depolarization-dependent Ca2+ entry and receptor-mediated responses in GH3 cells. Topical application of AGN 190742 or AGN 190744 inhibits neutrophil infiltration and epidermal hyperplasia induced by repeated treatment of mouse skin with phorbol ester. AGN 190744 also is active in an arachidonic acid model of acute inflammation. These data suggest that topical application of calcium-channel antagonists can inhibit cutaneous inflammatory responses and that AGN 190742 and/or AGN 190744 may serve as useful pharmacological probes for examining these responses in vivo.
De Vries
G W
GW
Department of Biological Sciences, Allergan, Inc., Irvine, California 92715, USA.
McLaughlin
A
A
Wenzel
M B
MB
Perez
J
J
Harcourt
D
D
Lee
G
G
Garst
M
M
Wheeler
L A
LA
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology; D004431:Ear, External; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009195:Peroxidase / Q000032:analysis; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000473:pathology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
C094473:AGN 190742; C094474:AGN 190744; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D013729:Terpenes; D016718:Arachidonic Acid; D013973:Thyrotropin-Releasing Hormone; D011189:Potassium Chloride; D002990:Clobetasol; D009195:Peroxidase; D010741:Phospholipases A; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C015429:phenidone; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium