Distribution and metabolism of the antipsychotic agent mazapertine succinate in rats

Caldwell, Gary W.; Wu, Wu‐Nan; McKown, Linda A.; Gauthier, Annick; Masucci, John A.; Jones, Walter W.; Leo, Gregory C.; Reitz, Allen B.

doi:10.1016/j.jpba.2005.10.052

Cited by 1 publication

(3 citation statements)

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“…Unchanged mazapertine plus ten metabolites were profiled, quantified, characterized, and tentatively identified by means of MS data. These metabolites were previously identified in rat and dog (6)(7)(8). API ionspray-MS and MSIMS exhibited apparent protonated molecular ions, and prominent, as well as important, fragment product ions for the structural elucidation of mazapertine, its metabolites and methyl derivatives.…”

Section: Resultsmentioning

confidence: 78%

“…int.) 179 (100), 178 (l O), 177 (8), 136 (83), 134 (6), 118 (7), 106 (6), and 85 (5) together with an intense MH+ at mlz 221 (26) (Figure 1). The structure of M 10 was tentatively assigned by means of MSIMS data and comparison of synthetic sample (RWJ-27315) (5).…”

Section: Enzyme Hydrolysismentioning

confidence: 98%

“…The in vitro metabolism of mazapertine in rat has been conducted and the identification of 12 metabolites has been reported (6). Mazapertine is well absorbed and extensively metabolized in rat and dog, and the excretion data and identification of more than 15 metabolites have been reported (7,8). The preliminary results on the psychopharmacological profiles, pharmacokinetics, and metabolism studies in healthy male volunteers have been reported (1- 4,9,10).…”

Section: Introductionmentioning

confidence: 99%

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Metabolic fate of the antipsychotic agent, mazapertine, in man — API-MS and MS/MS identification of urinary metabolites

McKown

Reitz

2007

European Journal of Drug Metabolism and Pharmacokinetics

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The in vivo metabolism of the antipsychotic agent mazapertine was studied after oral administration of mazapertine succinate (40 mg/subject) to two healthy volunteers, and urine (0-24 hours) was obtained for metabolite identification using API-ionspray LC/MS and MS/MS analysis. Unchanged mazapertine (12% of the sample) plus 10 metabolites were profiled, quantified, and tentatively identified on the basis of MS data, Glusulase-hydrolysis, and by comparison to synthetic samples. The formation of mazapertine metabolites are via seven metabolic pathways: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, (6). depiperidylation, and (7) glucuronidation. Pathways 1, 2, 5 and 7 formed 4-OH-phenyl-mazapertine (M1, 18%) and 4-OH-piperidyl (M2, 14%)-mazapertine, carboxybenzoylpiperidine (M8, 10%) and its glucuronide (M9, 14%) as four major metabolites. Six moderate and minor metabolites (M3-M7 & M10; each < or =10%) formed via a combination of pathways 1-6. Mazapertine is extensively metabolized in humans.

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Section: Resultsmentioning

confidence: 78%

Section: Enzyme Hydrolysismentioning

confidence: 98%