Antiproliferative effects on keratinocytes of a range of clinically used drugs with calmodulin antagonist activity.
Thirty-two drugs, including some in use for a variety of clinical disorders, were examined for their ability to inhibit calmodulin activity in vitro. From these, 10 drugs were selected for their inhibition of calmodulin activity and examined for their ability to inhibit proliferation of rapidly dividing human keratinocytes. A significant correlation between antiproliferative activity and calmodulin antagonist potency was found. Of these drugs there were several, including miconazole, dequalinium chloride, bromocriptine and tamoxifen, whose use is well established and well documented. The potential use of these drugs (and others identified in this way) as antipsoriatic agents is discussed.
Mac Neil
S
S
Department of Medicine, Northern General Hospital, Sheffield, U.K.
Dawson
R A
RA
Crocker
G
G
Tucker
W F
WF
Bittiner
B
B
Singleton
J G
JG
Hunter
T
T
Tierney
D F
DF
D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003868:Dequalinium / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008825:Miconazole / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology
D002147:Calmodulin; D013629:Tamoxifen; D008825:Miconazole; D003868:Dequalinium