Inhibition of cytochrome P450 2C9 activity in vitro by 5-hydroxytryptamine and adrenaline.

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Gervasini G, Martinez C, Agundez JA, Garcia-Gamito FJ, Benitez J

Inhibition of cytochrome P450 2C9 activity in vitro by 5-hydroxytryptamine and adrenaline.

Pharmacogenetics. 2001 Feb;11(1):29-37.

PubMed ID

11207028 [ View in PubMed

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Abstract

In the present study, the occurrence of a modulatory effect of 14 neurotransmitters, precursors and metabolites on the cytochrome P450 2C9 (CYP2C9) enzyme activity, as determined by diclofenac 4-hydroxylation, was studied in human liver microsomes. Two indoleamines, 5-hydroxytryptamine (5-HT) and adrenaline, showed a non-competitive-type inhibitory effect of approximately 90% of the diclofenac 4-hydroxylase activity, with Ki values of 63.5 (0.7 and 156 (89.3 microM, respectively. The rest of substances analysed were weak inhibitors or had no inhibitory effect. CYP2C subfamily is present in human brain, although CYP2C9 isozyme has not yet been identified in this tissue, and CYP2C9 is involved in the metabolism of psychoactive drugs. Therefore, the fact that endogenous compounds could modulate the CYP2C9 activity, suggests that an hypothetical local activity of brain CYP2C9 might be susceptible to regulatory mechanisms. The possible clinical implications of this modulation are discussed.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Epinephrine	Cytochrome P450 2C9	Protein	Humans	Unknown	Inhibitor	Details