CYP2D6
- Known as:
- CYP2D6
- Catalog number:
- ENZ-316
- Product Quantity:
- 5µg
- Category:
- -
- Supplier:
- Prospecbio
- Gene target:
- CYP2D6
Related genes to: CYP2D6
- Gene:
- CYP2D6 NIH gene
- Name:
- cytochrome P450 family 2 subfamily D member 6
- Previous symbol:
- CYP2DL1, CYP2D7P2, CYP2D7BP, CYP2D8P2, CYP2D7AP
- Synonyms:
- CPD6, P450-DB1, CYP2D, P450C2D
- Chromosome:
- 22q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-04-07
- Date modifiied:
- 2019-04-23
Related products to: CYP2D6
Related articles to: CYP2D6
- To provide an updated and integrative evaluation of duloxetine as a potential therapeutic agent for irritable bowel syndrome (IBS), with emphasis on its mechanisms of action across the gut-brain axis. The review addresses the key research question: Can duloxetine, beyond its antidepressant effects, modulate neuroimmune, microbial, and pharmacogenomic factors relevant to IBS, particularly pain-predominant subtypes? This narrative review provides a targeted synthesis of selected preclinical, clinical, and translational literature addressing duloxetine as a potential gut-brain axis modulator in irritable bowel syndrome. Evidence related to neuroimmune mechanisms, microbiota-related pathways, pharmacogenomic considerations, and clinical studies was narratively summarized. Evidence indicates that duloxetine modulates serotonergic and noradrenergic neurotransmission, decreases visceral hypersensitivity, and attenuates neuroinflammation via inhibition of microglial P2X4/NF-κB signaling. Duloxetine also shifts cytokine balance toward an anti-inflammatory profile (↑ IL-10, ↓ IL-6, ↓ TNF-α). Emerging data suggest additional benefits through modulation of gut microbiota composition, enhancement of short-chain fatty acid (SCFA) production, and improvement of intestinal barrier integrity. Pharmacogenomic factors, especially CYP2D6 and CYP1A2 polymorphisms, significantly influence duloxetine metabolism and therapeutic response. Compared with TCAs and SSRIs, duloxetine shows more favorable efficacy in relieving combined gastrointestinal and psychological symptoms with fewer sexual side effects. Duloxetine exhibits multifaceted actions that extend beyond mood regulation, positioning it as a promising but still investigational GBA-directed option dual-action therapy within the gut-brain axis framework. The collective findings support the need for biomarker-guided clinical trials incorporating microbiota profiling, cytokine signatures, and pharmacogenetic testing to validate duloxetine's role in precision-medicine-based IBS management. - Source: PubMed
Publication date: 2026/05/22
Rejili MokhtarMustafa Aya MAl-Kuraishy Hayder MHussein Nawar RAl-Maiahy Thabat JAl-Gareeb Ali IAlbuhadily Ali KBatiha Gaber El-Saber - We performed a retrospective cohort study to evaluate risk of antidepressant discontinuation as a function of CYP2C19 and CYP2D6 phenotype. Patients who participated in an elective genomic screening and had a diagnosis of depression or anxiety with a corresponding antidepressant were analyzed. This resulted in 5 808 patients comprising 8 571 antidepressant orders. Of the total antidepressant orders, 51% of the antidepressants ordered before pharmacogenetic testing were discontinued. A multivariate analysis - accounting for age, medication tenure, allergies, PHQ-9, malaise/fatigue, and medication indication - revealed a significant association between metabolizer status and discontinuation for CYP2C19 increased metabolizers (ultrarapid plus rapid metabolizers) compared to normal metabolizers (n = 4 635) (HR = 1.17 [1.08, 1.27], p < 0.001) for CPIC guideline-recommended medications (i.e., citalopram, escitalopram, sertraline). Stratifying risk by individual drug maintained significant associations for escitalopram (HR = 1.27 [1.1, 1.46], p < 0.05) and sertraline (HR = 1.15 [1.01, 1.31], p < 0.05). While the CYP2D6 decreased metabolizer group (intermediate plus poor metabolizers) did not reach statistical significance for guideline recommended medications (i.e., paroxetine, venlafaxine, vortioxetine), the individual effect for venlafaxine showed an increased risk of discontinuation (HR = 1.23 [1.01, 1.5], p < 0.05). These results suggest phenotypic variations may have variable impact on risk of discontinuation amongst different antidepressant medications, but for escitalopram, sertraline, and venlafaxine, the risk of discontinuation in particular phenotypes should be considered at the time of therapy initiation. - Source: PubMed
Publication date: 2026/05/21
Baye Jordan FPetry Natasha JHines LindsayWeaver MaxReinke MichaelBrady HalleMassmann AmandaSchultz April - T-2 toxin is a highly toxic mycotoxin commonly present in food and the environment, with accumulating evidence supporting its hepatotoxic potential. However, the molecular events linking T-2 toxin exposure to liver fibrosis remain insufficiently characterized. - Source: PubMed
Publication date: 2026/05/20
Qiao LichunShi ShaotengWang LiangjiaShafiq Muhammad AftabTang JingLi MiaoqianWan PingZhou JingxuanDai XuleiHan JingGuo Yijie - The human HepaRG cell line is the closest surrogate to primary culture of hepatocytes (PHH) for toxicology studies. However, differentiated HepaRG cells express low levels of the cytochrome P450 2D6 (CYP2D6) involved in the biotransformation of many drugs. Herein, progenitor HepaRG cells were transduced using lentiviral particles encoding both human CYP2D6 and GFP proteins. The resulting transgenic HepaRG cells stably expressed catalytically active CYP2D6 at levels close to those observed in PHH from rapid metabolizers and HepaSH™ hepatocytes. In CYP2D6 transgenic HepaRG cells, tramadol was metabolized into both N- and O-desmethyl tramadol as seen in humans while parental HepaRG cells produced only N-desmethyl tramadol. Following treatment with perhexiline, the CYP2D6 expressing HepaRG cells exhibited higher IC values and reduced mitochondrial damages compared to those found in parental cells. Transcriptomic analysis revealed that the expression of CYP2D6 did not significantly affect the cells' ability to proliferate and differentiate or compromise key hepatocyte-specific functions. However, we identified a small number of genes, including NXF3 and TRIM63, which were up-regulated in transgenic cells. Using CRISPR/Cas9-mediated knockdown of GFP and/or CYP2D6 sequences, we demonstrated that NXF3 mRNA and protein inductions were triggered by the lentiviral mRNA encoding GFP and CYP2D6 rather than by genomic transgene integration. Together, these findings establish CYP2D6-transgenic HepaRG™ cells as an optimized and reliable hepatocyte-like model for studying the metabolism and toxicity of CYP2D6 substrates. Our results also support the hypothesis that the NXF3 gene may be a marker of cellular response to the expression of a lentiviral chimeric mRNA. - Source: PubMed
Publication date: 2026/05/21
Coppens-Exandier HugoMackanga FranzDarde ThomasBonhomme CorentinAngenard GaëlleLeroyer PatriciaRibault CatherineGicquel ThomasPelletier RomainRoshchina FlyuzaSchaefer EstelleChesné ChristopheJamin AgnèsCorlu AnneLoyer Pascal - Analgesic effect from codeine is from its metabolite, morphine. Morphine is formed by the O-demethylation of codeine and that enzyme is controlled by the cytochrome P450 2D6. More than 60 alleles in the CYP2D6 gene have been identified. This spectrum of polymorphism can be categorized into four groups: poor (PM), intermediate (IM), normal (NM), and ultra-rapid (UR) metabolizers. Codeine is rarely used in children because of fears that those with the UR genotype may suffer respiratory depression from increased morphine production. There is also concern that postpartum women medicated with codeine and who are UR metabolizers may have enough morphine in breastmilk to cause respiratory depression in a breastfed neonate. A pharmacokinetic compartment model was used to explore this assumption. There are five issues to consider in the pharmacological pathway from maternal ingestion of codeine to neonatal morphine plasma concentration: maternal morphine concentration that is dependent on genotype, milk to plasma concentration ratio, neonatal codeine and morphine exposure from breastmilk, codeine metabolism to morphine in the neonate, and morphine clearance in the neonate. The compartment model confirmed the implausibility of neonatal opioid toxicity from breastfeeding. Currently, short-term maternal use of prescription opioids (other than codeine) is considered safe and infrequently presents a hazard to the newborn. Postpartum women are denied codeine for analgesia and yet predicted neonatal morphine concentrations are lower than 1 μg/L, regardless of genotype. Maternal opioids are used with caution, especially after multiple doses, and neonates younger than 46 weeks postmenstrual age are observed for drowsiness and respiratory depression. The maternal use of codeine requires similar considerations and the current ban on codeine use in postpartum women who are breastfeeding requires review. - Source: PubMed
Publication date: 2026/05/21
Anderson Brian JHannam Jacqueline A