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Paediatric clinical pharmacology
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The test has been applied to determining dextromethorphan phenotypes in paediatric patients with autoimmune hepatitis [26]. In a recent study 300 mcg/kg dextromethorphan was administered to a group of neonates through the first year of life [25]. Urine was collected into a nappy overnight. CYP2D6 phenotype consistent with genotype was achieved by 14.5 days postnatal age. The maturation of the CYP3A pathway (N-demethylation) was found to be delayed relative to CYP2D6. The use of this substrate in children is potentially problematic, especially in neonates and infants, because dextrorphan formation as a measure of CYP2D6 is dependent on renal function [52], which changes with developmental age. The ratio of dextromethorphan to dextrorphan also depends on urinary pH.
Overview of Neurotransmission: Relationship to the Action of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
It is interesting to note that a widely used drug, dextromethorphan (marketed as an antitussive) and its metabolite dextrorphan have been found to have NMDA receptor antagonist properties and are anticonvulsant.136-138 (See also Chapters 5 and 12.)
Mammalian CYP2D Members A Comparison of Structure, Function, and Regulation
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
In rats, dextromethorphan is metabolized to dextrorphan, 3-methoxymorphinan, and 3-hydroxymorphinan, with dextrorphan being the primary one (Kerry et al. 1993). Additionally, the O-demethylated metabolites dextrorphan and 3-hydroxymorphinan are subject to subsequent Phase II conjugating reaction (Kerry et al. 1993). Inhibition studies using known CYP2D6 inhibitors such as quinine, dextropropoxyphene, methadone, and propafenone have confirmed that the metabolism of dextromethorphan to dextrorphan is mostly via Cyp2ds in rats (Kerry et al. 1993). Conversion of dextromethorphan to dextrorphan via O-demethylation appears to be a suitable marker for Cyp2ds in rats.
Successful treatment of dextromethorphan use disorder with combined naltrexone and gabapentin: a case report
Published in The American Journal of Drug and Alcohol Abuse, 2023
Nicole Ledwos, Aurelia I. Andreiev, Tianna Costa, Nitin Chopra, Tony P. George
NyQuilTM is an over-the-counter medication containing the pain reliever, acetaminophen; the antihistamine, doxylamine; and dextromethorphan (DXM), the anti-tussive medication. The NyquilTM liquid formulation also contains alcohol, listed among the inactive ingredients. DXM has dependence-producing properties and addiction liability, especially in young people (1). Large doses (>1500 mg/day) can produce dissociative effects similar to ketamine (2). DXM is the methylated d-isomer of levorphanol, a substance related to codeine (3). The active metabolite, dextrorphan, is a noncompetitive NMDA-R antagonist and a sigma-1 receptor agonist (3). Interestingly, DXM overdose has been successfully treated with naloxone, a µ-opioid receptor antagonist (4). Given DXM’s mechanism of action at both NMDA and sigma-1 receptors, it may be possible to treat DXM addiction by targeting these receptors. Moreover, the anti-histamine doxylamine may contribute to the actions of NyquilTM. We present a case-report on DXM use disorder treated with the combination of naltrexone and gabapentin.
Effect of laparoscopic sleeve gastrectomy on drug pharmacokinetics
Published in Expert Review of Clinical Pharmacology, 2021
Kaifeng Chen, Yaqi Lin, Ping Luo, Nan Yang, Guoping Yang, Liyong Zhu, Qi Pei
Dextrorphan is the O-demethylated metabolite of dextromethorphan, which can be further N-demethylated to form 3-hydroxymorphinan (morphinan-3-ol) by CYP3A4 [32]. The effect of body mass index and bariatric surgery (LSG and RYGB) on CYP3A4 activity was investigated both prior to surgery and at 1 month and 6 months after surgery [17]. CYP3A4 activity was markedly lower in patients with extreme obesity than in normal-weight controls. This could be explained by the fact that the dextrorphan/3-hydroxymorphinan ratio (CYP3A4-mediated substrate/product ratio) had a positive correlation with BMI. Interestingly, bariatric surgery normalized CYP3A4 activity. Although such effects were observed in both surgical types, they occurred earlier in LSG (with statistical significance achieved at 4 weeks post-operation and maintained at 6 months) as opposed to RYGB (for which statistical significance was noted at 6 months after surgery).
AVP-786 as a promising treatment option for Alzheimer’s Disease including agitation
Published in Expert Opinion on Pharmacotherapy, 2021
Rita Khoury, Charlotte Marx, Sidney Mirgati, Divya Velury, Binu Chakkamparambil, George T. Grossberg
DM is a non-selective, non-competitive low affinity NMDAR antagonist [49]. In larger doses, dextrorphan, the metabolite of DM is a more potent antagonist of the NMDAR. Like ketamine and phencyclidine, it antagonizes the NMDAR by binding to the calcium cation channel [50]. However, the rapid unbinding from the channel open state and a favorable tolerability profile differentiate DM from high-affinity, slow-unblocking ligands such as phencyclidine and ketamine, which are associated with adverse events such as confusion, agitation, memory loss and hallucinations [33]. This characteristic NMDAR antagonist activity is similar to the one exhibited by memantine, and may explain the promising effect of DM in the treatment of agitation in AD and other dementias [51,52].