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Metabolism of N? -methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes.


ABSTRACT: The roots/rhizomes of black cohosh (Cimicifuga racemosa L. (Nutt.) (syn. Actaea racemosa L.) are a popular dietary supplements among women for management of menopausal symptoms. Although not estrogenic, N? -methylserotonin has been identified in black cohosh as a potent agonist of serotonin 5-HT1A and 5-HT7 receptors. In the present study, in vitro metabolism of N? -methylserotonin was investigated to gain insights into aspects of the bioavailability of this compound. The major metabolic pathway was determined to be conversion into 5-hydroxyindole acetaldehyde catalyzed by the monoamine oxidase A (MAO-A). 5-Hydroxyindole acetaldehyde could be further oxidized to form 5-hydroxyindole acetic acid by the action of microsomal aldehyde dehydrogenase or reduced to 5-hydroxy tryptophol by the action of aldehyde reductase. The cytochrome P450 enzymes had only a minor role in the metabolism of N? -methylserotonin and then only when MAO-A was inhibited. In many aspects, the metabolism of N? -methylserotonin was similar to the metabolism of serotonin, suggesting that this compound is unlikely to elicit CNS effects due to rapid metabolism by the widely distributed MAO-A.

SUBMITTER: Nikolic D 

PROVIDER: S-EPMC4229456 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Metabolism of Nω -methylserotonin, a serotonergic constituent of black cohosh (Cimicifuga racemosa, L. (Nutt.)), by human liver microsomes.

Nikolić Dejan D   Li Jinghu J   van Breemen Richard B RB  

Biomedical chromatography : BMC 20140512 12


The roots/rhizomes of black cohosh (Cimicifuga racemosa L. (Nutt.) (syn. Actaea racemosa L.) are a popular dietary supplements among women for management of menopausal symptoms. Although not estrogenic, Nω -methylserotonin has been identified in black cohosh as a potent agonist of serotonin 5-HT1A and 5-HT7 receptors. In the present study, in vitro metabolism of Nω -methylserotonin was investigated to gain insights into aspects of the bioavailability of this compound. The major metabolic pathway  ...[more]

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