PROSPECTS FOR A PROCEDURE FOR ASSESSING CYP2D6 ACTIVITY USING PINOLINE

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DOI: https://doi.org/None
Issue: 
5
Year: 
2015

R.Kh. Abdrashitov, G.N. Gildeeva, PhD; Professor G.V. Ramenskaya, PhD; V.V. Smirnov, PhD I.M. Sechenov First Moscow State Medical University; 8, Trubetskaya St., Build. 2, Moscow 119991

Cytochrome P450 isoenzymes are involved in the biotransformation of different endogenous an exogenous substances, including medications. The paper considers the specific features of the functioning and polymorphism of the cytochrome P-450 isoenzyme CYP2D6 and the possible consequences of its malfunction influenced by genetic factors and inhibitors or inducers. It also deals with the advantages, disadvantages, and limitations of existing procedures for determining its activity with exogenous markers. Screening studies of endogenous substrates that are prone to biotransformation that is predominantly affected by the isoenzyme CYP2D6 are reviewed. The compounds indole methylamine, 5-methoxy-N,Ndimethyltryptamine (5-MDMT) and pinoline (6-methoxy-1,2,3,4-tetrahydro-β-carboline) had the greatest affinity for CYP2D6. The specificity of pinoline was about 99%. The paper covers the results of investigations dealing with the relationship of pinoline to its metabolite 6-hydroxy-1,2,3,4tetrahydro-β-carboline in vitro on cell culture and in vivo in mice for further assessment of CYP2D6 activity.
Keywords: 
biotransformation
phenotyping
CYP2D6
cytochrome P450
pinoline
personalized medicine
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