Abstract:According to previous studies, R‐(‐)‐venlafaxine (VEN) has higher enantioselectivity than S‐(+)‐VEN, and the plasma concentration of R‐(‐)‐VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects of CYP2D6*10 genotypes on the steady‐state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O‐desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (P… Show more
“…The discovered properties of the JNK inhibitor can be used to develop a fundamentally new approach to personification and increase the effectiveness of venlafaxine antidepressant therapy [7,8]. Based on the identified phenomena, JNK inactivation in liver cells can increase the level of drug transformation in low metabolizers (persons with low CYP2D6 expression, or in patients with liver diseases [3,4,6]) to the normal level (i.e. in extensive metabolizers of venlafaxine).…”
Section: Resultsmentioning
confidence: 99%
“…In 30 min, the venlafaxine (Aarti Industries) was added to the homogenate in a dose of 100 ng/ml and the cell suspension was incubated at 37°C in a TS-100 thermoshaker (Biosan). In 30 min, 1, 2, and 4 h, the content of the main venlafaxine metabolite O-desmethylvenlafaxine (O-DVLF) was evaluated [6,7]. The control was liver homogenate containing equivalent amounts of venlafaxine and solvent (DMSO, final concentration of 0.15%).…”
Section: Methodsmentioning
confidence: 99%
“…This psychotropic pharmaceutical (presented by a racemate of R-and S-enantiomers) is one of the most effective modern antidepressants; its therapeutic effect is realized via blockade of serotonin, norepinephrine, and dopamine reuptake [9]. However, its low efficiency in some cases [3,5,6] requires the development of personalized approaches to venlafaxine therapy, including modification of its pharmacokinetics and pharmacodynamics [1].…”
We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism.
“…The discovered properties of the JNK inhibitor can be used to develop a fundamentally new approach to personification and increase the effectiveness of venlafaxine antidepressant therapy [7,8]. Based on the identified phenomena, JNK inactivation in liver cells can increase the level of drug transformation in low metabolizers (persons with low CYP2D6 expression, or in patients with liver diseases [3,4,6]) to the normal level (i.e. in extensive metabolizers of venlafaxine).…”
Section: Resultsmentioning
confidence: 99%
“…In 30 min, the venlafaxine (Aarti Industries) was added to the homogenate in a dose of 100 ng/ml and the cell suspension was incubated at 37°C in a TS-100 thermoshaker (Biosan). In 30 min, 1, 2, and 4 h, the content of the main venlafaxine metabolite O-desmethylvenlafaxine (O-DVLF) was evaluated [6,7]. The control was liver homogenate containing equivalent amounts of venlafaxine and solvent (DMSO, final concentration of 0.15%).…”
Section: Methodsmentioning
confidence: 99%
“…This psychotropic pharmaceutical (presented by a racemate of R-and S-enantiomers) is one of the most effective modern antidepressants; its therapeutic effect is realized via blockade of serotonin, norepinephrine, and dopamine reuptake [9]. However, its low efficiency in some cases [3,5,6] requires the development of personalized approaches to venlafaxine therapy, including modification of its pharmacokinetics and pharmacodynamics [1].…”
We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism.
“…CYP2D6 is involved in the metabolism of 5-HT in the brain, which is linked to psychiatric disorders, as well as the synthesis of serotonin and dopamine [ 90 ]. Among these alleles, *10 is a mutation with a high allele frequency in Asian populations [ 91 ]. A study on patients with recurrent depression found that an SNP in CYP2D6 was associated with the efficacy of the antidepressant duloxetine [ 92 ].…”
Background:
Genetic polymorphism has been proven to have an important association with depression, which can influence the risk of developing depression, the efficacy of medications, and adverse effects via metabolic and neurological pathways. Nonetheless, aspects of the association between single nucleotide polymorphisms and depression have not been systematically investigated by bibliometric analysis.
Objective:
The aim of this study was to analyze the current status and trends of single nucleotide polymorphism research on depression through bibliometric and visual analysis.
Methods:
The Web of Science Core Collection was used to retrieve 10,043 articles that were published between 1998 and 2021. CiteSpace (6.1 R4) was used to perform collaborative network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection.
Results:
The most productive and co-cited journals were the Journal of Affective Disorders and Biological Psychiatry, respectively, and an analysis of the references showed that the most recent research focused on the largest thematic cluster, "5-HT", reflecting the important research base in this area. "CYP2D6" has been in the spotlight since its emergence in 2009 and has become a research hotspot since its outbreak in 2019. However, "BDNF," "COMT," "older adults," "loci," and "DNA methylation" are also the new frontier of research, and some of them are currently in the process of exploration.
Conclusion:
These findings offer a useful perspective on existing research and potential future approaches in the study of the association between single nucleotide polymorphisms and depression, which may assist researchers in selecting appropriate collaborators or journals.
“…However, the specific roles of individual signal transduction pathways in regulating the xenobioticmetabolizing function of cells competent in this regard are largely unknown. Simultaneously, uncovering the involvement and distinct roles of particular signaling molecules in the biotransformation of pharmacologically active substances can form the basis for the development of innovative approaches to personalized pharmacotherapy [7][8][9][10][11]. Therefore, it is pertinent to investigate the potential for controlling the intensity and nature of substance transformation within the body by regulating intracellular signal transduction in metabolizing cells and creating 'Targeted Regulators of Xenobiotic/Drug Metabolism' [7,12].…”
The effect of the c-Jun N-terminal kinases (JNK) inhibitor 'IQ-1' on the pharmacokinetics of the antidepressant venlafaxine was studied. An acceleration of the metabolism of this psychotropic agent was revealed when a modifier of intracellular signal transduction was administered to experimental animals in vivo. The JNK blockade was accompanied by a decrease in the plasma level of the antidepressant without changes in the concentration of the pharmacologically active metabolite O-desmethylvenlafaxine. The results obtained indicate a modification of the pattern of venlafaxine biotransformation, involving a change in metabolic pathways with an increase in the formation of other metabolites, or a correction of its distribution in the body. The revealed properties of the JNK inhibitor can be used to develop fundamentally new approaches to improve the effectiveness of antidepressant therapy with venlafaxine within the framework of implementing the 'Strategy for Targeted Regulation of Xenobiotic Metabolism and Drug Pharmacokinetics'.
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