Hepatic metabolism of the new antipsychotic agent, mazapertine, in rat — API-MS/MS identification of metabolites

被引：0
作者：
W. N. Wu
L. A. McKown
A. B. Reitz
机构：
[1] L.L.C.,Johnson & Johnson Pharmaceutical Research & Development
来源：
European Journal of Drug Metabolism and Pharmacokinetics | 2003年 / 28卷
关键词：
Mazapertine; antipsychotic agent; rat hepatic S9; in vitro metabolism; ms/ms;
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学科分类号：
摘要：
The In vitro biotransformation of the antipsychotic agent, mazapertine was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged mazapertine (42% of the sample) plus 12 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS data. The proposed metabolic pathways for mazapertine are proposed, and the 6 metabolic pathways are: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, and (6) dehydration. Pathways 1 to 3 formed 4-OH-phenyl (M1, 10%) and 4-OH-piperidyl (M2, 9%)-mazapertine, O-desisopropyl mazapertine (M3, 17%), and N-desbenzoylpiperidine-mazapertine (M8, 14%) as 4 major metabolites. Mazapertine is extensively metabolized in rat hepatic S9 fraction.
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页码：279 / 286
页数：7
相关论文
共 42 条
[1]  
Buclin T.(1993)Tolerance, psychopharmacological profile and pharmacokinetics of a new neuroleptic, mazapertine (RWJ-37796), in healthy volunteers Schweizerische Medizinische Wochenschrift 123 39-39
[2]  
Stucki R.(1994)A new arypiperazine antipsychotic with high D J. Med. Chem. 37 1060-1062
[3]  
Jaquet-Mueller F.(1997)/D Bioorganic & Medicinal Chemistry Letters 7 1927-1930
[4]  
Munafo A.(1994)/5-HT Pharm. Res. 11 336-336
[5]  
Bauldauf C.(1998)/α Pharm. Scitm Supplement 1 PS36-PS36
[6]  
Brunner-Ferber F.(1993)-adrenergic affinity and a low potential for extrapyramidal effects Pharm. Res. 10 398-398
[7]  
Piquet V.(2000)The synthesis and evaluation of the major metabolites of mazapertine J. Pharm. Biomed. Anal. 24 307-316
[8]  
Biollaz J.(1999)Metabolism and excretion of the antipsychotic agent, RWJ-37796 in rats Xenobiotica 29 453-466
[9]  
Reitz A.B.(undefined)In vitro metabolism of the novel antipsychotic agent, mazapertine succinate (RWJ-37796) in rat hepatic S9 fraction undefined undefined undefined-undefined
[10]  
Bennet D.J.(undefined)The effect of food on the bioavailability (BA) of a new antipsychotic drug (RWJ-37796) undefined undefined undefined-undefined
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