Abstract |
Dipfluzine hydrochloride (Dip), a novel diphenylpiperazine calcium channel blocker, has revealed the characteristics of a promising candidate for the treatment of cerebral vascular diseases in preclinical studies. Our research identified and quantified Dip and its 4 metabolites (M1, M2, M4 and M5) in rat liver microsomes by liquid chromatography tandem mass spectrometry. The results showed that Dip was firstly metabolized to M1 and M5 by 1- and 4-dealkylation from a piperazine nitrogen, and then the latter was subsequently metabolized to M2 and M4. The concentrations of Dip, M1, M2 and M5 were 557.3 ± 26.3, 854.3 ± 46.0, 2796.7± 126.9, 2473.3 ± 82.6 and 4.0 ± 0.4, 2.4 ± 0.1, 318.2 ± 8.7 and 27.4 ± 1.5 ng/ml in male and female rats, respectively. M4 (404.2 ± 22.2 ng/ml) was detected only in males not in females, suggesting that there is gender difference in the metabolism of Dip.
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Authors | Wei Guo, Dezhi Kong, Yingfeng Du, Xiaowei Shi, Wei Wang, Yongli Wang |
Journal | Pharmacology
(Pharmacology)
Vol. 89
Issue 3-4
Pg. 201-10
( 2012)
ISSN: 1423-0313 [Electronic] Switzerland |
PMID | 22473133
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
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Copyright | Copyright © 2012 S. Karger AG, Basel. |
Chemical References |
- Calcium Channel Blockers
- Cinnarizine
- dipfluzine
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Topics |
- Animals
- Calcium Channel Blockers
(metabolism)
- Chromatography, Liquid
(methods)
- Cinnarizine
(analogs & derivatives, metabolism)
- Female
- Male
- Microsomes, Liver
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reproducibility of Results
- Sex Factors
- Tandem Mass Spectrometry
(methods)
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