Reproducibility of the In Vivo Effect of the Selective Serotonin Reuptake Inhibitors on the In Vivo Function of Cytochrome P450 2D6: An Update (Part I)

2003 ◽  
Vol 9 (2) ◽  
pp. 150-158 ◽  
Author(s):  
SHELDON H. PRESKORN
Keyword(s):  
Cytochrome P450 ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

An Amperometric Cytochrome P450-2D6 Biosensor System for the Detection of the Selective Serotonin Reuptake Inhibitors (SSRIs) Paroxetine and Fluvoxamine

2016 ◽  
Vol 44 ◽  
pp. 208-228 ◽  
Author(s):  
Rachel Fanelwa Ajayi ◽  
Ezo Nxusani ◽  
Samantha F. Douman ◽  
Anovuyo Jonnas ◽  
Priscilla Gloria Lorraine Baker ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Competitive Inhibition ◽  
Plasma Concentrations ◽  
Antidepressant Drug ◽  
Selective Serotonin ◽  
Cytochrome P450 2D6 ◽  
Biosensor System ◽  
P450 2D6

Paroxetine is the second most prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drug, characterized by extensive inter-individual variation in steady state plasma concentrations resulting in drug toxicity amongst patinets. A nanopolymeric biosensor for studying the biotransformation of paroxetine is presented. The bioelectrode system consists of cytochrome P450-2D6 enzyme encapsulated in nanotubular poly (8-anilino-1-napthalene sulphonic acid) electrochemically deposited on gold. The biosensing procedure involved the determination of the extent of modulation of fluvoxamine responses to the P450-2D6 enzyme electrode after incubation in paroxetine standard solutions. Paroxetine inhibited the activity of cytochrome P450-2D6 (CYP2D6) resulting in a decrease in the fluvoxamine signal of the biosensor. The biosensor gave a linear analytical response for the paroxetine in the interval 0.005 and 0.05 μM, with a detection limit of 0.002 μM and a response time of 30 s. Electrochemical Michaelis–Menten kinetics of the reversible competitive inhibition of the fluvoxamine responses of the biosensor by 0, 0.05 and 0.1 μM paroxetine gave apparent Michaelis–Menten constant (KMapp) values of 1.00 μM, 1.11 μM and 1.25 μM, respectively. The corresponding value for the maximum response, IMAX was 0.02 A. The dissociation constant, KI, value evaluated from Dixon analysis of the paroxetine modulation data was estimated to be-0.02 μM while Cornish-Bowden analysis confirmed the competitive inhibitory characteristics of the enzyme.

Debate resolved: there are differential effects of serotonin selective reuptake inhibitors on cytochrome P450 enzymes

1998 ◽  
Vol 12 (4_suppl) ◽  
pp. S89-S97 ◽  
Author(s):  
Sheldon H. Preskorn
Keyword(s):  
Cytochrome P450 ◽  
Plasma Levels ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Original Position ◽  
Selective Serotonin ◽  
Cytochrome P450 Enzymes ◽  
Extensive Body ◽  
Cyp 2D6

In 1993, it was first proposed that an important difference between selective serotonin reuptake inhibitors (SSRIs) was the degree of inhibition of the cytochrome P450 (CYP) enzyme 2D6 that they produced under usually dosing conditions (Preskorn, 1993). Specifically, fluoxetine and paroxetine, in contrast to sertraline, were identified as causing substantial increases in the plasma levels of coadministered drugs, which were principally dependent on CYP 2D6 for their metabolism. Over the next 5 years, this position was hotly contested (Preskorn and Nemeroff, 1997). However, an extensive body of research has now accumulated, which incontrovertibly supports the original position. This paper will reviews this research and extends the discussion to all five SSRIs and four other important CYP enzymes: 1A2, 2C9/10, 2C19, and 3A3/4.

scholarly journals Inhibitory and Stimulatory Effects of Selective Serotonin Reuptake Inhibitors on Cytochrome P450 2D6-mediated Dopamine Formation from p-Tyramine

2019 ◽  
Vol 22 ◽  
pp. 585-592
Author(s):  
Toshiro Niwa ◽  
Shizuya Sugimoto
Keyword(s):  
Cytochrome P450 ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Maximal Velocity ◽  
Cyp2d6 Polymorphism ◽  
Amine Metabolism ◽  
Michaelis Constants ◽  
The Brain

PURPOSE: The effects of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine on dopamine formation from p-tyramine, mediated by cytochrome P450 (CYP) 2D6.2 (Arg296Cys, Ser486Thr) and CYP2D6.10 (Pro34Ser, Ser486Thr), were compared with their effects on CYP2D6.1 (wild type)-mediated dopamine formation, to investigate the influence of a CYP2D6 polymorphism on neuroactive amine metabolism in the brain. METHODS: The Michaelis constants (Km) and maximal velocity (Vmax) values of dopamine formation mediated by CYP2D6.1, CYP2D6.2, and CYP2D6.10 (expressed in recombinant Escherichia coli), and inhibition constants (Ki) of the SSRIs toward dopamine formation catalyzed by the CYP2D6 variants were estimated. RESULTS: The Km values for CYP2D6.2 and CYP2D6.10 decreased at lower fluoxetine concentrations, while the Vmax values for all CYP2D6 variants increased, indicating that fluoxetine stimulated dopamine formation. Conversely, paroxetine competitively inhibited dopamine formation mediated by CYP2D6.1, CYP2D6.2, and CYP2D6.10 with Ki values of 0.47, 1.33, and 31.3 µM, respectively. CONCLUSIONS: These results suggest that the inhibition/stimulation of CYP2D6

Cytochrome P450 genotype and aggressive behavior on selective serotonin reuptake inhibitors

2018 ◽  
Vol 19 (14) ◽  
pp. 1097-1099
Author(s):  
Corine Ekhart ◽  
Maja Matic ◽  
Agnes Kant ◽  
Laure Elens ◽  
Eugène van Puijenbroek ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aggressive Behavior ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin
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