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
- N,N-Dimethyltryptamine (DMT) is a naturally occurring substituted tryptamine used as a psychedelic drug for ritual purposes by various cultures. Derivatives were already found on the drug of abuse market, such as N-tert-butoxycarbonyl-N,N-dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name DMT-isopropylcarbamate, DMT-pivaloylamide, and DMT-THP (N,N-dimethyl-2-[1-(oxan-2-yl)indol-3-yl]ethanamine). In vitro and in vivo metabolism studies with pooled human liver S9 incubations and zebrafish embryos were performed, respectively. Monooxygenase and monoamine oxidase (MAO) isozymes involved in the phase I metabolism were identified. In vitro metabolic stability and plasma protein binding (PPB) were evaluated. A total of 11 metabolites for DMT-Boc, 13 for DMT-isopropylcarbamate, eight for DMT-pivaloylamide and 16 for DMT-THP were identified using high-resolution tandem mass spectrometry. N-Demethylation and hydroxylation were the most relevant metabolic reactions. CYP1A2, CYP2D6, and FMO3 were identified as most active phase I isozymes and MAO-A contributed to DMT-THP metabolism. The in vitro half-lives of DMT-Boc, DMT-isopropylcarbamate, and DMT-pivaloylamide were calculated to be between 74 and 79 min, while that of DMT-THP was found to be > 180 min. All compounds showed high PPB (> 99%) indicating that co-consumption with other drugs might increase the DMT derivatives' toxicity. Combined in vitro and in vivo approaches provided a comprehensive metabolism overview. N, N-bis-Demethylated, N-demethylated and N-oxygenated metabolites along with parent compound were proposed as consumption markers in order to support clinical and forensic toxicologists to identify these substances in biosamples in case of suspected abuse. - Source: PubMed
Publication date: 2026/09/21
Daziani GloriaWagmann LeaKroesen Matthias DWellenberg K SimonGrill MatthiasHerrmann JenniferCarlier JérémyBusardò Francesco PaoloMeyer Markus R - Agitation and aggression in Alzheimer's disease (AD) are highly distressing behavioral symptoms traditionally managed with off-label atypical antipsychotics, despite boxed warnings for increased mortality in elderly patients. The emergence of Auvelity (dextromethorphan-bupropion) provides a critical, non-antipsychotic therapeutic alternative. - Source: PubMed
Sarangal MridulSarangal CharmiVora JaySoni Karishma - A series of 1,4-diaryl-1,3-dihydro-2H-imidazole-2-thione derivatives was designed and synthesized as anticonvulsant candidates, integrating AMPAR antagonism, neuronal Na1.2 channel blockade, and antioxidant neuroprotection. Biological screening identified compound 6a as the lead analogue, producing complete protection in the MES model at 100 mg/kg and 80% protection in the PTZ model, with a 24-fold prolongation of seizure-onset latency compared to PTZ-group. Quantitative evaluation showed an MES ED of 11.03 mg/kg, close to phenytoin, but with a markedly wider protective index (45.3 vs 6.89) and no neurotoxicity up to (TD > 500 mg/kg). Mechanistically, 6a inhibited AMPARs more potently than phenytoin and comparable to GYKI-52466 (IC = 12.7 ± 0.4 vs 30.0 ± 4.0 μM, 8.7 ± 0.4 μM, respectively) and blocked Na1.2 channels with higher potency than phenytoin (IC = 7.01 ± 1.1 vs 13.2 ± 2.0 μM), while showing negligible NMDAR liability. Compound 6a also showed excellent PAMPA-BBB permeability, minimal CYP3A4, CYP2D6, and CYP2C9 inhibition, and improved hepatic safety. Importantly, oral/i.p. PK profiling established its oral CNS exposure advantage: orally administered 6a reached serum C 4-fold faster than phenytoin, increased brain C by 3.16-fold, elevated brain AUC by 1.92-fold, and improved the brain/serum AUC ratio by 2.28-fold. Oral brain exposure exceeded the AMPAR and VGSC IC values by 6.38- and 11.57-fold, respectively, confirming pharmacologically relevant target coverage. Together, these findings identify compound 6a as a brain-penetrant AMPAR/Na1.2-modulating anticonvulsant lead. - Source: PubMed
Publication date: 2026/09/11
Mahmoud ShahendaEl-Moselhy Tarek FEl-Bastawissy Eman AAbo El Nasr Nesma M EElbaset Marawan AIbrahim Mahmoud A AKhan ShahzebAbalkhail TaradBarygin Oleg IZhigulin Arseniy SFurman Vitalina VKarelina Tatiana VHuang SunZamponi Gerald WSidhom Peter A - Atomoxetine is a selective norepinephrine reuptake inhibitor commonly prescribed for attention-deficit/hyperactivity disorder. Most overdoses are mild to moderate; however, severe neurologic and cardiovascular toxicity can occur. We report the case of a 21-year-old woman who ingested approximately 9720 mg of atomoxetine, corresponding to 174 mg/kg. She presented with generalized convulsive status epilepticus, hyperthermia, and severe lactic metabolic acidosis. Arterial blood gas analysis immediately after intubation showed pH 6.94, PaCO₂ 37 mmHg, HCO₃ 7.9 mmol/L, base excess -24.3 mmol/L, and lactate 16.0 mmol/L. After airway protection, activated charcoal was administered. Electrocardiography demonstrated marked QRS prolongation, followed by wide-complex ventricular tachycardia. During this episode, 250 mL of 7% sodium bicarbonate solution (approximately 208 mEq) and 2 g of magnesium sulfate were administered. Sinus rhythm returned within minutes, and subsequent electrocardiography showed QRS narrowing. Norepinephrine was used transiently for hypotension after deep sedation and was discontinued approximately 3 h after arrival. Serial plasma atomoxetine concentrations confirmed marked systemic exposure, with the peak concentration of 36,838 ng/mL approximately 4.5 h after ingestion. The patient was discharged ambulatory and without neurologic sequelae. Severe atomoxetine overdose may cause convulsive status epilepticus, profound lactic acidosis, and life-threatening cardiac conduction disturbances. Early airway protection, seizure control, continuous electrocardiographic monitoring, and consideration of sodium bicarbonate therapy for marked QRS widening are critical management strategies. - Source: PubMed
Publication date: 2026/09/14
Kyan RyokoChiba TakuyoMiyamoto MasatoshiAbe HirokoNagayama TomohisaNaito YusukeKamijo Yoshito - Imrecoxib is a cyclooxygenase-2-preferential nonsteroidal anti-inflammatory drug approved in China for the symptomatic treatment of osteoarthritis and is currently marketed only in China. This narrative review evaluates its clinical pharmacokinetics, including disposition, special populations, drug-drug interactions, and evidence for dose adjustment. After oral administration, imrecoxib reaches peak plasma concentrations within 2-3 h, and food increases systemic exposure. It is highly protein bound and extensively metabolised sequentially from imrecoxib (M0) to 4'-hydroxymethylimrecoxib (M1), then to the aldehyde intermediate 4'-formylimrecoxib (M-CHO), and finally to 4'-carboxyimrecoxib (M2). Cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) mediate M1 formation, while M2 formation also involves aldehyde oxidase. Both M1 and M2 are pharmacologically active, and M2 is the predominant circulating metabolite. Unchanged urinary excretion is negligible, whereas M1, M2, and their conjugates contribute to renal elimination. Severe renal impairment markedly increases M2 exposure (area under the plasma concentration-time curve from time zero to the last measurable concentration [AUC] approximately 3.7-fold that in subjects with normal renal function) and reduces its apparent clearance to approximately 37% of that in subjects with normal renal function, although the clinical exposure-response consequences and the proposed reduced-dose regimens remain unvalidated. Moderate hepatic impairment markedly increases imrecoxib and M1 exposure (area under the plasma concentration-time curve from time zero to infinity [AUC] approximately 10.8-fold and 3.2-fold that in matched healthy subjects, respectively), while M2 AUC increases by approximately 35%. In a small single-dose study, exposure to imrecoxib, M1, and M2 was numerically higher in older subjects, but the differences were not statistically significant and pharmacokinetic equivalence was not demonstrated. Currently, no definitive dose-adjustment recommendations have been established, although dose reduction may be considered in severe renal impairment; routine age-based adjustment is not supported, and the optimal regimen in hepatic impairment remains undefined. Multiple-dose imrecoxib did not meaningfully alter warfarin pharmacokinetics or anticoagulant response, whereas fluconazole increased imrecoxib maximum plasma concentration (Cₘₐₓ) and AUC by approximately 88% and 72%, respectively, without comparable increases in M1 or M2 exposure. Current evidence is limited by small, mainly single-dose studies, predominantly Chinese populations, and the absence of validated exposure-response relationships integrating imrecoxib, M1, and M2. More robust studies are needed to define dose adjustment in organ impairment. - Source: PubMed
Publication date: 2026/09/17
Zhao ShengnanLi CharlieMallillin Marlon CLöbenberg RaimarDavies Neal M