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Inhibition of TRPM3 channel by anti‐depressant and anti‐psychotic drugs
Author(s) -
Majeed Yasser,
Naylor Jacqueline,
Zeng Fanning,
Jones Clare,
Beech David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.937.5
Subject(s) - imipramine , chemistry , pharmacology , chlorpromazine , endogeny , drug , trpm2 , hek 293 cells , transient receptor potential channel , receptor , biochemistry , medicine , alternative medicine , pathology
TRPM3 is a member of the TRP super‐family of cation channels about which relatively little is known (Oberwinkler 2007 Handb Exp Pharmacol 179, 253–67). Putatively it is a novel chemical‐sensing channel and thus we have searched for chemicals that affect TRPM3, either as endogenous modulators or pharmacological agents. For these experiments we used tetracycline‐inducible human TRPM3‐ or TRPM2‐expressing HEK 293 cells studied using fura‐2 to measure calcium‐entry in real‐time 96‐well plate assays. Because TRPM3 is expressed in the nervous system we investigated anti‐psychotic and depressant drugs. The anti‐depressants imipramine and fluoxetine caused concentration‐dependent inhibition, showing IC 50 s of 91 μM and 42 μM respectively. Neither drug had effect on TRPM2 or the endogenous ATP response of the cells. The anti‐psychotic drug chlorpromazine was also inhibitory on TRPM3 (IC 50 28 μM) and TRPM2, but not on the ATP response. The effects of these drugs on TRPM3 may have clinical relevance or indicate lead compounds for the development of potent TRPM3 blockers.