Effect of antidepressants on cytochrome P450 (CYP) 2D6-mediated dopamine formation from p-tyramine

Toshiro Niwa, Mayumi Yanai, Shizuya Sugimoto, Marina Shizuku
2019 Proceedings for Annual Meeting of The Japanese Pharmacological Society  
Purpose] CYP2D catalyze dopamine formation from pand m-tyramine in the brain, and human CYP2D6 is polymorphic Imipramine, a tricyclic antidepressant, and fluvoxamine, an SSRI, are CYP2D6 inhibitors. Dopamine formation from p-tyramine mediated by CYP2D6 variants, CYP2D6.2 and CYP2D6.10 was compared, and the effect of genetic polymorphism on the inhibitory effects of antidepressants was investigated. [Methods] CYP2D6.1, CYP2D6.2, and CYP2D6.10 expressed in recombinant Escherichia coli were used.
more » ... ia coli were used. Dopamine formation from p-tyramine in the presence of antidepressants such as imipramine, desipramine, fluvoxamine, fluoxetine, and paroxetine was determined by HPLC. [Results] CYP2D6.10 had higher Michaelis constants of dopamine formation than CYP2D6.1 and CYP2D6.2. Inhibition constant of imipramine and desipramine against CYP2D6.10 were higher than that against CYP2D6.1. Fluoxetine and paroxetine inhibited CYP2D6.1-mediated dopamine formation. The maximal velocity for all CYP2D6 variants gradually increased with increasing fluvoxamine concentrations. [Conclusions] CYP2D6 polymorphism might affect the inhibitory effect of antidepressants on dopamine formation in the brain. Poster Sessions
doi:10.1254/jpssuppl.92.0_3-p-128 fatcat:kbl5j2cw65ce7cfbbqgjzj2lmi