Ask about this productRelated genes to: CYP2D6 antibody
- 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 antibody
Related articles to: CYP2D6 antibody
- Tramadol is frequently co-prescribed with oxycodone or hydrocodone after surgery under the assumption that its dual mechanism of action provides an opioid-sparing benefit. However, evidence supporting this practice is limited and inconsistent. We conducted a secondary analysis of the multicenter IGNITE ADOPT-PGx pragmatic trial of patients undergoing elective surgery who were prescribed oxycodone alone (n = 317) versus tramadol + oxycodone (n = 96), or hydrocodone alone (n = 563) versus tramadol + hydrocodone (n = 42). Co-primary outcomes of this study were cumulative morphine milligram equivalents (MME) consumed during the 10 days following surgery and composite pain scores at day 10 defined as the sum of current pain and average and worst pain in the past 7 days (score ranges from 3 to 15). Inverse probability of treatment weighting (IPTW) was used to adjust for demographic characteristics, comorbidities, and concomitant analgesics. Sensitivity analyses restricted to CYP2D6 normal metabolizers and sites prescribing both monotherapy and combination therapy and subgroup analysis including total knee arthroplasty patients were conducted. Compared to oxycodone alone, the combination of oxycodone and tramadol was associated with higher MME (adjusted mean 205.2 vs 122.5; P < 0.0001) and lower mobility, without meaningful differences in pain scores (adjusted mean 9.6 vs 9.4; P = 0.41). Similar findings were observed for hydrocodone-only vs hydrocodone + tramadol groups. Results were consistent in sensitivity and subgroup analyses. Co-administration of tramadol with oxycodone or hydrocodone was associated with substantially higher total MME and reduced mobility without any demonstrable improvement in pain control. - Source: PubMed
Publication date: 2026/08/17
Nahid Noor ASoliman Ahmed IBaye Jordan FPetry Natasha JGray Chancellor FMyers Rachel AElwood Erica NHarris Elizabeth CChakraborty HrishikeshVolpi SimonaRider ReneeDexter Paul RPeterson Josh FSkaar Todd CParvataneni Hari KCavallari Larisa HJohnson Julie A - Epilepsy remains a major neurological disorder in need of safer and more effective antiepileptic agents. In this study, nineteen nafimidone-guided derivatives were designed, synthesized, and biologically evaluated to identify new anticonvulsant leads with improved efficacy, brain accessibility, and safety. Initial in vivo screening in the MES model identified compounds 11b and 12a among the most active derivatives, both affording 100% protection against MES-induced seizures at 30 mg/kg. Quantitative anticonvulsant testing established 12a as the most potent lead, with an ED₅₀ of 3.12 mg/kg and a protective index >160.3, exceeding both nafimidone (ED₅₀ 7.40 mg/kg; PI 16.56) and phenytoin (ED₅₀ 6.14 mg/kg; PI 18.3), while 11b showed an ED₅₀ of 14.31 mg/kg and PI >34.94. Electrophysiological studies confirmed effective Na1.2 blockade, with 12a showing the highest potency (IC₅₀ = 16.93 ± 1.33 μM) versus11b (31.21 ± 1.88 μM) and nafimidone (43.12 ± 1.27 μM), together with preferential inactivated-state inhibition. Both compounds restored seizure-associated neurochemical imbalance in PTZ-kindled brains, increasing GABA by 365% (11b) and 353% (12a) and reducing glutamate by 28%, outperforming nafimidone. Oxidative stress was also markedly attenuated, as reflected by increased GSH (+38% and + 40%) and reduced MDA (-43% and -41%) for 11b and 12a, respectively. In vitro antioxidant assays revealed a distinct antioxidant activity for 11b, which showed strong FRAP activity (1458.90 ± 6.86 μM TE/mg), whereas 12a displayed minimal radical-scavenging activity, indicating a more channel-focused profile. Importantly, both leads exhibited favorable CNS drug-like behavior, with high PAMPA-BBB permeability and efficient in vivo brain exposure; 12a showed the highest brain/plasma ratios (3.42 at 0.25 h and 3.97 at 0.5 h). Both compounds also showed minimal CYP3A4, CYP2D6, and CYP2C9 inhibition at 50 μM, reduced Na1.5-related liability, and improved cytotoxic and hepatotoxic profiles relative to nafimidone and phenytoin, with 12a showing the most favorable hepatic safety pattern. Collectively, these findings identify 12a as the most promising anticonvulsant lead, combining potent Na1.2-targeted seizure protection, excellent brain exposure, improved CYP inhibition profile, and reduced hepatic liability, while 11b emerges as a complementary dual-action scaffold with stronger antioxidant activity and PTZ-protective features. - Source: PubMed
Publication date: 2026/08/09
Mahmoud ShahendaF El-Moselhy TarekA El-Bastawissy EmanSalama AbeerIbrahim Mahmoud A AKhan ShahzebPentlavalli SreekanthAbalkhail TaradSalih Mohammed A MHuang SunZamponi Gerald WSidhom Peter A - Hypoxic pregnancy promotes fetal growth restriction (FGR) and preterm birth, for which antenatal corticosteroids (ACS) are recommended to prevent respiratory distress. Adults born FGR or preterm are at greater risk of health conditions requiring medication(s), which are metabolised by hepatic cytochrome P450 (CYP) enzymes. We determined if ACS and/or hypoxic pregnancy alters fetal and adult offspring hepatic CYP activity. Ewes carrying singletons were randomly allocated to normoxic (Nx) or hypoxic (Hx; 11% O) pregnancy from 105-138 dGA (term = 147 dGA). Dexamethasone (Dex, 12mg IM) or vehicle (saline IV) was administered at 115 and 116 dGA. Ewes carrying male fetuses were humanely killed at 138 ± 2 dGA, while female fetuses lambed spontaneously and were humanely killed at 9 months (9 mo). Hepatic CYP activity was quantified using functional assays, and expression of glucocorticoid signalling and CYP regulating proteins was determined via Western blot. Hx increased fetal hepatic CYP2B6 and CYP2D6 activity, expression of 11β-HSD1&2 and reduced GRα-A nuclear expression, and cytosolic GRβ:α-A ratio. Dex reduced fetal CYP3A metabolism of testosterone to metabolites 6β-OHT and 2α-OHT, and GRα-A and GRβ cytosolic expression. Fetal CYP2B6 activity positively correlated with CAR in Nx, but not Hx. In 9 mo lambs, Hx reduced CYP2C19 activity and PPARα and GRβ cytosolic expression. Dex decreased CYP1A2, CYP2B6, CYP2E1 activity, and CYP3A testosterone metabolism to 6β-OHT. HxDex increased cytosolic and nuclear GRβ:α-A. Hx and Dex differentially effect hepatic CYP activity in offspring, and changes to CYP activity may be due to a loss of regulatory control. - Source: PubMed
Publication date: 2026/08/13
Bennett Millicent G AMeakin Ashley SBotting-Lawford Kimberley JNiu YouguoFord Sage GWiese Michael DGiussani Dino AMorrison Janna L - Postoperative sleep disturbance (PSD) is a common yet underrecognized complication after breast cancer surgery and is associated with pain, fatigue, affective symptoms, impaired quality of life, and delayed postoperative recovery. Its management remains challenging because symptom presentations are clinically heterogeneous, and treatment decisions must balance therapeutic efficacy with safety within the broader context of breast cancer care and survivorship. This narrative review summarizes the current evidence on PSD after breast cancer surgery, with particular emphasis on pharmacologic management, therapeutic positioning, and breast cancer-specific safety considerations. Available evidence suggests that a phenotype-guided pharmacologic management framework may be clinically useful, although this approach remains conceptual and has not yet been prospectively validated in postoperative breast cancer populations. Short-course hypnotics may be considered for acute insomnia characterized by prominent nocturnal hyperarousal, whereas melatonin and melatonin receptor agonists may be particularly relevant when circadian disruption predominates. In contrast, gabapentinoids and multimodal analgesic strategies may be more appropriate for pain-dominant or mixed symptom presentations. Across drug classes, treatment selection should account for cumulative sedative burden, respiratory risk associated with concurrent opioid use, next-day cognitive adverse effects, and endocrine therapy context, including avoidance of strong CYP2D6 inhibitors in patients receiving tamoxifen. Among non-pharmacologic interventions, cognitive behavioral therapy for insomnia (CBT-I) is best positioned as the leading adjunctive strategy, particularly for persistent symptoms or during medication de-escalation. Bright light therapy, exercise-based rehabilitation, mindfulness-based interventions, and acupuncture may provide selective supportive benefits in appropriately selected patients, although their roles are generally complementary rather than primary. Overall, PSD after breast cancer surgery should be recognized as a clinically meaningful component of postoperative recovery and survivorship care. Future studies should prioritize standardized sleep outcomes, objective monitoring where feasible, clearer phenotype definition, and integrated efficacy-safety assessment to support more individualized and mechanism-informed management. - Source: PubMed
Publication date: 2026/07/29
Bu FanZeng ShulinLiu QinzheLou ZhengchiMa ChaoPeng YuemingXiong LileWen YiQin Lan - Cancer pain affects more than half of all oncology patients and represents one of the most challenging therapeutic problems in modern medicine. Despite the central role of opioids in cancer pain management-codified by the WHO analgesic ladder-the clinical response to these agents is highly variable between individuals. Pharmacogenomics promises to explain this heterogeneity by identifying functionally relevant genetic polymorphisms in genes encoding opioid receptors, metabolizing enzymes, and membrane transport proteins. However, after two decades of intensive research, clinical translation of genetic data into actionable prescribing strategies remains elusive. A narrative-critical review of the literature was conducted by searching PubMed, Scopus, and Web of Science databases from inception to March 2026, using the search terms "opioid," "pharmacogenomics," "pharmacogenetics," "cancer pain," "polymorphism," and individual gene names (OPRM1, CYP2D6, COMT, ABCB1, SLC22A1, UGT2B7, and others). Reference lists of included articles were hand-searched for additional relevant studies. Inclusion was restricted to English-language articles reporting original data or systematic reviews on genetic polymorphisms and opioid response, with priority given to studies conducted in cancer pain populations. Clinical practice guidelines from CPIC, NCCN, ESMO, EAPC, and ASCO were consulted for current recommendations. This narrative-critical review examines the evidence on genetic polymorphisms relevant to opioid response in cancer pain, covering three functional categories: (1) pharmacodynamic genes, including opioid receptors (OPRM1, OPRD1, OPRK1) and neuromodulatory targets (COMT, KCNJ6, MC1R); (2) pharmacokinetic enzymes (CYP2D6, CYP3A4/5, UGT2B7); and (3) membrane transporters, including ABC efflux pumps (ABCB1, ABCG2, ABCC2) and SLC uptake carriers (SLC22A1, SLCO1B1, SLC6A4, SLC6A2). A dedicated section addresses the direct and indirect interference of the tumour itself-through the tumour microenvironment, neuroimmune signalling, epigenetic reprogramming, and cancer-induced organ dysfunction-on opioid pharmacogenomics. The overall evidence is poor and fragmented, a finding intrinsic to the extraordinary diversity, large number, and context-dependent biological activity of the polymorphisms identified. The tumour itself acts as a pervasive confounder that systematically distorts genotype-phenotype relationships. The path forward requires a paradigm shift from candidate-gene association studies to system pharmacogenomics and multi-omic integration. - Source: PubMed
Publication date: 2026/08/04
Mercadante Sebastiano