Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is an "atypical" antipsychotic agent with a high affinity for serotonin 5HT2A/C, 5HT3, 5HT6, and dopamine D1, D2, D3, D4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant medications. Imipramine pharmacokinetics serve as a marker for hepatic CYP2D6, CYP1A2, CYP3A activity. An open-label, three-way randomized crossover study was done to determine the safety, pharmacokinetics, and potential for a drug interaction between olanzapine (5 mg) and imipramine (75 mg). Each drug was administered alone and in combination. Nine healthy men, ages 32 to 54 years, enrolled in the study. Psychomotor performance capacities, plasma olanzapine, imipramine, desipramine concentrations, and clinical laboratory tests were measured. Pharmacokinetic variables, vital signs, subjective tests for liveliness, and psychomotor outcomes were analyzed using a two-way ANOVA. Olanzapine was safe. Sedation, postural hypotension, and minor vital sign alterations occurred during all treatments. On the liveliness questionnaire, patients generally reported poorer (less lively) scores with olanzapine alone or coadministered with imipramine versus baseline scores. These effects disappeared within 24 hours after administration. Olanzapine alone and in combination decreased motor-speed tasks (finger tapping and visual-arm random reach) compared with baseline or imipramine treatment. Peak 6-hour changes were statistically significant but clinical importance was only marginal. Olanzapine concentrations were < 19% greater than with imipramine. But olanzapine did not affect the kinetics of imipramine or desipramine and, therefore, did not show a metabolic drug interaction involving CYP2D6.
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PMID:Olanzapine: interaction study with imipramine. 950 89

The metabolism of the structurally related 5HT3 antagonists ondansetron, alosetron and GR87442 in the rat, dog and human was determined in hepatocytes, liver microsomes and human recombinant microsomes. The profiles of phase I metabolites were similar in human hepatocytes and microsomes. The metabolites of all three compounds produced in rat, dog and human microsomes and hepatocytes were similar to those seen in vivo, with the major routes of metabolism being N-dealkylation and/or hydroxylation. There was more extensive metabolic processing in hepatocytes than in microsomes; however, sequential metabolism was less extensive in vitro compared with in vivo. The pharmacokinetics of the three 5HT3 antagonists investigated were dominated by CYP3A4 (and/or 2C9) compared with CYP1A2 in man, possibly determined by enzyme capacity rather than relative enzyme affinity. These data support the use of rat, dog and human hepatocytes for the prediction of in vivo metabolites of ondansetron, alosetron and GR87442.
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PMID:The metabolism of the 5HT3 antagonists ondansetron, alosetron and GR87442 I: a comparison of in vitro and in vivo metabolism and in vitro enzyme kinetics in rat, dog and human hepatocytes, microsomes and recombinant human enzymes. 1770 32