Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs

Shin, Eun Joo; Bach, Jae Hyung; Lee, Sung Youl; Kim, Jeong‐Min; Lee, Jinhwa; Hong, Jau–Shyong; Nabeshima, Toshitaka; Kim, Hyoung Chun

doi:10.1254/jphs.11r02cr

Cited by 32 publications

(29 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DM also protects monoaminergic neurons against inflammation-mediated degeneration (Liu and Hong 2003) and endotoxicity (Liu and Hong 2003;Zhang et al 2004;Zhang et al 2005). Apart from its being an NMDA receptor, DM and its metabolite may stimulate sigma-1 receptor, inhibit serotonin reuptake, and block L-type calcium channel mediating anti-inflammation, anti-convulsive, anti-parkinsonian, anti-ischemic, antioxidant, and alleviation of pseudobulbar effects (Chen 2011;Shin et al 2011). Above evidence suggests that DM offers promising neuroprotective and anti-inflammatory benefits in neurodegenerative disorders such as are BD.…”

mentioning

confidence: 99%

Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial

Lee

Wang

Chang

et al. 2020

Int J Bipolar Disord

Self Cite

View full text Add to dashboard Cite

Background: The aim of this study is to determine whether adding combination of agents with anti-inflammatory and neurotrophic effects is more efficacious than mood stabilizer alone in improving clinical symptoms, plasma brainderived neurotrophic factor (BDNF), cytokine levels, and metabolic profiles in patients with bipolar spectrum disorder. Methods:In a randomized, double-blind, controlled 12-week clinical trial, patients with moderate mood symptoms (HDRS ≥ 18 or YMRS ≥ 14) were recruited. The patients were randomly assigned to a group while still undergoing regular valproate (VPA) treatments: VPA + dextromethorphan (DM) (30 mg/day) + memantine (MM) (5 mg/day) (DM30 + MM5) (n = 66), VPA + DM (30 mg/day) (DM30) (n = 69), VPA + MM (5 mg/day) (MM5) (n = 66), or VPA + Placebo (Placebo) (n = 69). Symptom severity, immunological parameters [plasma tumor necrosis factor (TNF)-α and C-reactive protein (CRP)] and plasma brain-derived neurotrophic factor (BDNF) were regularly examined. Metabolic profiles [cholesterol, triglycerides, glycosylated hemoglobin (HbA1C), fasting serum glucose, body mass index (BMI)] were measured at baseline and at 2, 8, and 12 weeks.Results: Depression scores were significantly (P = 0.03) decreases and BDNF levels significantly (P = 0.04) increased in the DM30 + MM5 group than in the Placebo group. However, neither depressive scores nor BDNF levels were significantly different between the DM30, MM5, and Placebo groups. Changes in certain plasma cytokine and BDNF levels were significantly correlated with metabolic parameters. Conclusion:We concluded that add-on DM30 + MM5 was significantly more effective than placebo for clinical symptoms and plasma BDNF levels. Additional studies with larger samples and mechanistic studies are necessary to confirm our findings.Trial registration NCT03039842 (https ://regis ter.clini caltr ials.gov/). Trial date was -Retrospectively registered, https ://clini caltr ials.gov/ct2/show/NCT03 03984 2?term=NCT03 03984 2&rank=1.

show abstract

mentioning

confidence: 99%

Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial

Lee

Wang

Chang

et al. 2020

Int J Bipolar Disord

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dextromethorphan (DM, 3-methoxy-17-methylmorphinan) is a typical morphine like opioid, which is derived from levorphanol17. DM is known for its acceptable safety and efficacy profiles with no sedative or addictive properties at recommended antitussive doses1819. It is also a relatively selective and specific NMDA receptor antagonist and reported to inhibit serotonin uptake into neurons20212223.…”

mentioning

confidence: 99%

“…It is also a relatively selective and specific NMDA receptor antagonist and reported to inhibit serotonin uptake into neurons20212223. Base on its pharmacological effects, DM is used for treating pseudobulbar affect (PBA, a common manifestation of brain pathology associated with many neurological diseases)24 and prescribed as a neuroprotective agent for seizures, cerebral ischemia and Parkinson’s disease19. Although DM have been reported for its protect effect on methamphetamine-induced neurotoxicity in vivo 25, it remains unclear whether DM has neuroprotective effects against MDMA-induced damage in cerebral SERT changes.…”

mentioning

confidence: 99%

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Hsing

Liu

Weng

et al. 2016

Sci Rep

View full text Add to dashboard Cite

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

show abstract

“…Dextromethorphan (DM), a derivative of morphinan, is one of the most widely used non-opioid cough suppressants, acting as the active ingredient in numerous antitussive formulations (13). As an antitussive, DM is superior to opioids used at antitussive doses in that DM lacks any gastrointestinal side effects, such as constipation, and produces a lower degree of depression of the CNS.…”

Section: Introductionmentioning

confidence: 99%

Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide-stimulated BV2 microglia

Cheng

Hou

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflammation-mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor-κB (NFκB), caspase-3 signaling and the expression of another inflammation-inducing factor, heat shock protein 60 (HSP60) and heat shock factor-1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti-inflammatory effect by inhibiting microglial activation through the HSP60-NFκB signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation.

show abstract

Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs

Cited by 32 publications

References 89 publications

Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial

Combination of dextromethorphan and memantine in treating bipolar spectrum disorder: a 12-week double-blind randomized clinical trial

Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide-stimulated BV2 microglia

Contact Info

Product

Resources

About