Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia

Sang, Christine N.; Booher, Susan; Gilron, Ian; Parada, Suzan; Max, Mitchell B.

doi:10.1097/00000542-200205000-00005

Cited by 223 publications

(157 citation statements)

References 38 publications

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“…However, this condition has particular symptomatic characteristics that may account, in part, for its response to treatment. For instance, the NMDA antagonist dextromethorphan and the anti-epileptic lacosamide have no effect on this condition, whereas they have been found effective for other neuropathic pain syndromes (22,29,32).…”

Section: Discussionmentioning

confidence: 99%

Neuropathic pain: Are there distinct subtypes depending on the aetiology or anatomical lesion?

Attal

Fermanian

et al. 2008

Pain

258

145

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Section: Discussionmentioning

confidence: 99%

Neuropathic pain: Are there distinct subtypes depending on the aetiology or anatomical lesion?

Attal

Fermanian

et al. 2008

Pain

258

145

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“…It has been clearly shown in animal studies that various NMDA antagonists [4,12], including memantine [42], if administered in a manner that blocks NMDA receptors, can relieve neuropathic pain. In a clinical trial [59] in which memantine was administered to neuropathic pain patients for 9 weeks at doses titrated to the individual patient's level of tolerance, the maximum tolerated dose was 55 mg/day. This was the dose at which subjectively-determined disagreeable side effects began to occur, but at this dose there was no relief of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain

Creeley

Wozniak

Nardi

et al. 2008

Neurobiology of Aging

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The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer's disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine's neurotoxic potential has not been investigated. In the present study, we determined that a dose of memantine (20 mg/kg ip), considered to be in the therapeutic (neuroprotective) range for rats, causes a mild neurotoxic reaction in the adult rat brain. Co-administration of memantine (20 or 30 mg/kg) with donepezil (2.5 to 10mg/kg) markedly potentiated this neurotoxic reaction, causing neuronal injury at lower doses of memantine, and causing the toxic reaction to become disseminated and lethal to neurons throughout many brain regions. These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process.

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“…It has been shown repeatedly in animal studies that various NMDA antagonists (Davar et al, 1991;Backonja et al, 1994), including memantine (Neugebauer et al, 1993;Eisenberg et al, 1995), if administered at a dose that blocks NMDA receptors, can relieve neuropathic pain. In a clinical trial in which memantine was administered to neuropathic pain patients for 9 weeks at doses titrated to the individual patient's level of tolerance, the maximum tolerated dose was 55 mg/d (Sang et al, 2002). This was the dose at which subjectively determined disagreeable side effects began to occur, but, at this dose, there was no relief of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Low Doses of Memantine Disrupt Memory in Adult Rats

Creeley¹,

Wozniak²,

Labruyere³

et al. 2006

J. Neurosci.

120

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Memantine, a drug recently approved for treatment of Alzheimer's disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptormediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose that we found, contrary to previous reports, produces locomotor disturbances severe enough to preclude testing for learning and memory effects. We then determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts both memory and locomotor behaviors. Rats treated with these doses performed at control-like levels in learning a hole-board task but were significantly impaired in demonstrating what they had learned when tested 24 h later. This impairment of memory retention was not state dependent in that it was demonstrable regardless of whether the rats were or were not exposed to memantine on the day of retention testing. We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment.

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Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia

Abstract: Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.

Cited by 223 publications

References 38 publications

Neuropathic pain: Are there distinct subtypes depending on the aetiology or anatomical lesion?

Neuropathic pain: Are there distinct subtypes depending on the aetiology or anatomical lesion?

Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain

Low Doses of Memantine Disrupt Memory in Adult Rats

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