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Analyses of The Urate‐lowering Effects by Zotepine and Chlorprothixene
Author(s) -
Onizawa Nobuyuki,
Izeki Tatou,
Hori Takayuki,
Otani Naoyuki,
Ouchi Motoshi,
Hasegawa Hajime,
Anzai Naohiko
Publication year - 2015
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.29.1_supplement.845.25
Subject(s) - benzbromarone , chemistry , uricosuric , hyperuricemia , pharmacology , reabsorption , probenecid , uric acid , renal physiology , xanthine oxidase , biochemistry , renal function , medicine , enzyme , organic chemistry , sodium
Zotepine and chlorprothixene are antipsychotic drugs, and they have a broad therapeutic effect on patients with schizophrenia. Zotepine and chlorprothixene have been reported to decrease serum uric acid levels. In addition, increase in renal clearance of uric acid was reported in several studies. However, the molecular mechanism underlying these effects has not yet been clarified. Here, we sought to elucidate the molecular mechanism underlying the urate‐lowering effects of zotepine and chlorprothixene. Methods: We measured [ 14 C] urate uptake by using stable cells expressing the human urate transporter (HEK‐URAT)1 and mock cells (HEK‐mock), to evaluate the uricosuric action of zotepine and chlorprothixene. Next, we measured the activity of human xanthine oxidase (XO) to ascertain if zotepine and chlorprothixene have inhibitory effects on urate production. Results: Zotepine and chlorprothixene inhibited URAT1‐mediated urate uptake. In contrast, urate production mediated by XO was not inhibited. Conclusions URAT1, a major contributor of renal urate reabsorption and a major target of uricosuric drugs such as losartan and benzbromarone, interacted with zotepine and chlorprothixene; however, XO, a major enzyme for urate production in the body, did not interact with zotepine and chlorprothixene. These results suggest that the urate‐lowering effects of zotepine and chlorprothixene are mainly associated with the inhibition of renal urate reabsorption via renal urate transporters such as URAT1.