Dextromethorphan as a Potential Neuroprotective Agent With Unique Mechanisms of Action

Werling, Linda L.; Lauterbach, Edward C.; Calef, Ursula

doi:10.1097/nrl.0b013e3180f60bd8

Cited by 76 publications

(65 citation statements)

References 103 publications

(262 reference statements)

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“…DM has already proven its therapeutic potential in different neonatal brain damage models like excitotoxicity and hypoxiaischemia [204][205][206] . It has numerous neuroactive properties including high-affinity σ1 receptor agonism, lowaffinity N-methyl-D -aspartate receptor (NMDAR) antagonism, and voltage-gated calcium channel antagonism, with additional anti-inflammatory and antioxidative qualities [207] . In 6-day-old rats exposed to 24 h of hyperoxia, a single dose (5 or 25 μg/kg of body weight) of DM significantly reduced apoptosis on immunohistochemistry.…”

Section: Hormonesmentioning

confidence: 99%

Hyperoxia and the Immature Brain

et al. 2016

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Despite major advances in obstetrics and neonatal intensive care, preterm infants frequently suffer from neurological impairments in later life. Preterm and also full-term neonates are generally susceptible to injury caused by reactive oxygen species due to the immaturity of endogenous radical scavenging systems. It is well known that high oxygen levels experienced during the critical phase of maturation can profoundly influence developmental processes. Supraphysiological oxygen concentrations used for resuscitation or in the care of critically ill infants are known to have deleterious effects on the developing lung and retina, contributing to the pathophysiology of neonatal diseases like bronchopulmonary dysplasia and retinopathy of prematurity. Moreover, experimental work from the last decade suggests that hyperoxia also leads to neuronal and glial cell death, contributing to the injury of white and grey matter observed in preterm infants. During the critical phase of brain maturation, hyperoxia can alter developmental processes, resulting in the disruption of neural plasticity and myelination. However, oxygen therapy can often not be avoided in neonatal intensive care. Therefore, in situations requiring oxygen supplementation, in addition to the development of appropriate monitoring systems, protective and/or regenerative strategies are highly warranted. Here, we summarise the clinical and experimental evidence as well as potential therapeutic strategies, providing an overview of the pathophysiology of oxygen exposure on the developing central nervous system and its impact on neonatal brain injury.

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Section: Hormonesmentioning

confidence: 99%

Hyperoxia and the Immature Brain

et al. 2016

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“…Innovation in this field is therefore a high priority. Treatment with dextromethorphan and quinidine has been proposed due to their mechanistic antagonism of nicotinic α3β4 receptor and low-affinity N -methyl-D-aspartate and inhibition of serotonin and norepinephrine reuptake,4 in addition to preliminary evidence of benefit to agitation in other patients.…”

Section: Contextmentioning

confidence: 99%

Dextromethorphan and quinidine are suitable for off-label short-term treatment of agitation in people with Alzheimer's disease following first-line non-drug approaches

Corbett

Ballard

2015

Evid Based Med

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“…Significantly, more recent double-blind trials have confirmed that DM can improve motor function in PD patients, especially the dyskinesia associated with long-term levadopa treatment (Verhagen Metman, Blanchet et al 1998;Verhagen Metman, Del Dotto et al 1998). It has been suggested that the uncertainty over the true effects of DM might be due to the relatively rapid metabolism of DM in vivo (Werling, Lauterbach et al 2007). Although, DX and other DM metabolites have shown similar neuroprotective properties in preclinical studies, only DM seems to function through multiple mechanisms rather than simply blocking activity of the NMDA-receptor (Werling, Lauterbach et al 2007).…”

Section: Morphinan-based Anti-inflammatory Therapeuticsmentioning

confidence: 99%

“…It has been suggested that the uncertainty over the true effects of DM might be due to the relatively rapid metabolism of DM in vivo (Werling, Lauterbach et al 2007). Although, DX and other DM metabolites have shown similar neuroprotective properties in preclinical studies, only DM seems to function through multiple mechanisms rather than simply blocking activity of the NMDA-receptor (Werling, Lauterbach et al 2007). In situ DM concentrations can be increased if given in conjunction with a low dose of the drug quinidine which retards metabolism of DM and leads to increased DM concentrations in plasma, resulting in greater bioavailability (Pope, Khalil et al 2004).…”

Section: Morphinan-based Anti-inflammatory Therapeuticsmentioning

confidence: 99%