CYP2D in the brain
Yoshihiko Funae, Wataru Kishimoto, Toshio Cho, Toshiro Niwa, Toyoko Hiroi
Drug Metabolism and Pharmacokinetics2003
Summary (paraphrased)
This review surveys CYP2D isoforms in the brain: in rats CYP2D4 mRNA is most abundant in cerebellum, striatum, pons and medulla, while in humans only CYP2D6 is expressed, highest in cerebellum. It reports that CYP2D enzymes metabolize both xenobiotics (antidepressants, beta-blockers, antiarrhythmics) and endogenous substrates, that CYP2D6 alone among 11 tested human P450s efficiently converts tyramine to dopamine, and that CYP2D4/CYP2D6 carry steroid 21-hydroxylase activity for progesterone and allopregnanolone in the brain. The authors conclude brain CYP2D participates in neuronal amine/steroid metabolism and CNS regulation.
Why it’s in the corpus
Highly relevant pharmacogenetic context: CYP2D6 metabolizes many SSRIs/SNRIs and converts tyramine to dopamine, and it hydroxylates neurosteroids like allopregnanolone — implicating CYP2D in both the dopamine signaling deficits and neurosteroid disruption discussed in PSSD/PFS theories.
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