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

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).

Metabolism of the new anxiolytic agent, a pyrido[1,2-]benzimidazole (PBI) analog (RWJ-53050), in rat and human hepatic S9 fractions, and in dog; identification of cytochrome p450 isoforms mediated in the human microsomal metabolism.

The in vitro and in vivo metabolism of RWJ-53050, an anxiolytic agent, was investigated after incubation with rat and human hepatic S9 fractions, and human microsomes and 7 microsomes containing individual human CYP isoforms, CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 in the presence of NADPH-generating system, and a single oral dose administration to dogs (30 mg/kg). Unchanged RWJ-53050 (> or = 74% of the sample in vitro; < or = 13% in vivo) plus 16 metabolites were profiled, quantified and tentatively identified based on the API-MS and MS/MS data. The formation of RWJ-53050 metabolites are via the 5 pathways: 1.

Distribution and metabolism of the antipsychotic agent mazapertine succinate in rats.

The pharmacokinetics and drug disposition of 14C 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoy]piperidine succinate (RWJ-37796, mazapertine, Mz) have been investigated in male and female Sprague-Dawley rats. Approximately 93% of the orally administered radioactive dose (30 mg/kg) was recovered after 7 days. Fecal elimination accounted for approximately 63% of the dose while urine accounted for 30%.

In-vitro metabolism of isotetrandrine, a bisbenzylisoquinoline alkaloid, in rat hepatic S9 fraction by high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry.

The objective of this study was to investigate the in-vitro metabolism of isotetrandrine, a bisbenzylisoquinoline alkaloid, using rat hepatic S9 fraction and to profile and identify its metabolites using high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry (HPLC-MS) and tandem mass spectrometry (MS/MS). Isotetrandrine was incubated at a concentration of 100 microg mL(-1) with male rat hepatic S9 fraction in the presence of an NADPH generating system (Tris buffer, pH 7.4, 37 degrees C).

N-alkyl-4-[(8-azabicyclo[3.2.1]-oct-3-ylidene)phenylmethyl]benzamides, micro and delta opioid agonists: a micro address.

The tertiary amide delta opioid agonist 2 is a potent antinociceptive agent. Compound 2 was metabolized in vitro and in vivo to secondary amide 3, a potent and selective micro opioid agonist. The SAR of a series of N-alkyl-4-[(8-azabicyclo[3.

In-vitro metabolism of the new anxiolytic agent, RWJ-50172, in rat hepatic S9 fraction and microbial transformation in fungi, Cunninghamella sp.

The in-vitro biotransformation of the anxiolytic agent, RWJ-50172 was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system, and incubating with Cunninghamella echinulata in soy-bean medium. Unchanged RWJ-50172 (80% of the sample in rat; 86% in fungi) plus 6 metabolites (M1-M6) were profiled, quantified and tentatively identified on the basis of API-MS/MS data. The metabolic pathways for RWJ-50172 are proposed, and the four metabolic pathways are: pyrido-oxidation (pathway A), phenylhydroxylation (B), dehydration (C) and reduction (D).

Hepatic biotransformation of the new calcium-mimetic agent, RWJ-68025, in the rat and in man--API-MS/MS identification of metabolites.

The in-vitro biotransformation of a new calcium-mimetic agent and benzenemethanamine analogue, RWJ-68025, was studied after incubation with rat and human hepatic S9 fractions in the presence of an NADPH-generating system. Unchanged RWJ-68025 (44-48% of the sample) plus 12 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS and MS/MS data, and ethyl derivatization for phenolic and carboxylic metabolites. Four metabolic pathways for RWJ-68025 were proposed: pathway 1, O-demethylation; pathway 2, phenyl oxidation; pathway 3, methyl oxidation; and pathway 4, N-dealkylation/acetylation.

In vitro metabolism of the new anxiolytic agent, RWJ-52763 in human hepatic S9 fraction-API-MS/MS identification of metabolites.

The in vitro metabolism of the anxiolytic agent, RWJ-52763 was studied after incubation with human hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged RWJ-52763 (64% of the sample) plus six metabolites (M1-M6) were profiled, quantified, and tentatively identified on the basis of API-MS/MS data. The metabolic pathways for RWJ-52763 are proposed, and the two metabolic pathways are: (1) N/O-dealkylation, and (2) phenylhydroxylation.

The in vitro metabolism of thalicarpine, an aporphine-benzyltetrahydroisoquinoline alkaloid, in the rat. API-MS/MS identification of thalicarpine and metabolites.

The in vitro metabolism of an antitumor, hypotensive, and antimicrobial aporphine-benzyltetrahydroisoquinoline alkaloid, thalicarpine was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged thalicarpine (46% of the sample) plus eight metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS/MS data. The proposed metabolic pathways for thalicarpine are proposed, and the three metabolic pathways are: (1) N-demethylation; (2) aporphine ring oxidation; and (3) benzylic oxidation/reduction.

Oral administration of cyclopentane neuraminidase inhibitors protects ferrets against influenza virus infection.

Several cyclopentane inhibitors of influenza virus neuraminidase that have inhibitory activities in tissue culture similar to those of zanamivir and oseltamivir have recently been described. These new inhibitors have been examined for efficacy against a virulent H3N2 influenza virus when administered orally to infected ferrets. Preliminary studies indicated that oral administration of BCX-1923, BCX-1827, or BCX-1812 (RWJ-270201) at a dose of 5 or 25 mg/kg of body weight was active in ferrets in reducing respiratory and constitutional signs and symptoms, but these antivirals affected virus titers in the upper and lower respiratory tracts only marginally.