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SSRIs and possible catecholamine depletion

Posted by ed_uk on February 16, 2005, at 9:42:23

Fluoxetine (Prozac) and paroxetine (Seroxat, Paxil) are inhibitors of CYP2D6.

From a UK government report....

It has recently been shown that CYP2D6 is involved in the metabolism of endogenous
amines that may be precursors of neurotransmitters such as dopamine. Theoretically, in extensive metabolisers of CYP2D6, drug administration may lead to inhibition of this P450 isoform with a consequent effect on endogenous metabolites, possibly leading to a relative deficiency of catecholamines in crucial areas of the brain. The relevance of this with respect to underlying personality, psychiatric disease and the pharmacology of the drugs used to treat these diseases is unclear and needs further investigation.

Yu AM, Idle JR, Herraiz T, Kupfer A, Gonzalez FJ. Screening for endogenous
substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.
Pharmacogenetics 2003;13(6):307-19.

Yu AM, Idle JR, Gonzalez FJ. Polymorphic cytochrome P450 2D6: humanized
mouse model and endogenous substrates. Drug Metabolism Reviews
2004;36(2):243-77.

Ed.


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