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Biotech / Medical : Neurobiological Tech (NTII) -- Ignore unavailable to you. Want to Upgrade?

To: VikingWarrior who wrote (524)	4/28/1999 8:22:00 AM
From: Dr. John M. de Castro	Read Replies (2) \| Respond to of 1494

Memantine: An Investigational Drug for the Alleviation of Neuropathic Pain - From issue No. 246 (March, 1998) of Medical Sciences Bulletin Issue 246 Memantine is an orally available N-methyl-D-aspartate (NMDA) antagonist that currently is undergoing clinical trials in patients with neuropathic pain. In a recent phase II clinical trial, memantine subjects with painful diabetic neuropathy experienced significant reductions in pain compared with placebo-treated subjects. Memantine was not effective in controlling pain in subjects with postherpetic neuralgia. How It Works Memantine acts as a neuroprotective agent. The NMDA receptor is linked to a voltage-responsive channel that responds to activation by opening and allowing the passage of ions. Calcium ions passing into the cell through the channel can lead to neurotoxicity and neuronal cell death. Antagonists of the NMDA receptor-channel complex have been shown to inhibit prophylactically or therapeutically enhanced feelings of pain caused by nerve damage. Memantine blocks the NMDA-associated ion channel in a noncompetitive manner and prevents passage of positively charged ions through the channel. Clinical Tips A number of studies have investigated the effect of memantine on pain in rats. In one study, memantine was the most effective NMDA antagonist in a rat model of chronic nerve injury pain. In this study, memantine produced 96% of its maximum effect in relieving pain at a dose level that did not cause motor impairment in rats. In a study examining the effectiveness of memantine in arthritic rats, it was shown to reduce response to both noxious and innocuous pressure. Memantine also has been shown to be an effective prophylactic treatment in rat models of pain. Pretreatment with memantine inhibited carrageenan-induced thermal hypersensitivity in rats, although it had no effect when administered therapeutically in this study. In addition, memantine was the second-most effective NMDA antagonist in the formalin paw test, a model of pain prevention in the rat. Another study showed that rats treated with memantine for 7 days using mini-osmotic pumps showed a decreased response to pain both during the treatment period and for 3 days after the treatment period ended. A recent phase II clinical study has shown that diabetic subjects with neuropathic pain experienced 29% greater pain relief than placebo-treated subjects. Levels of daytime pain decreased by 18%, and nighttime pain decreased by 30%. In contrast, subjects with postherpetic neuralgia did not experience pain relief beyond that experienced by placebo- treated subjects. A National Institutes of Health (NIH)-sponsored study testing the efficacy of memantine in patients with AIDS dementia complex and neuropathic pain is ongoing. Published reports indicate that memantine also may be effective in the treatment of Parkinson's disease and acquired pendular nystagmus in patients with multiple sclerosis. References 1.Carlton SM, Hargett GL. Treatment with the NMDA antagonist memantine attenuates nociceptive responses to mechanical stimulation in neuropathic rats. Neurosci Lett. 1995;198:115-118. 2.Chaplan SR, Malmberg AB, Yaksh TL. Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J Pharmacol Exp Ther. 1997;280:828-838. 3.Eisenberg E, LaCross S, Strassman AM. The effects of the clinically tested NMDA receptor antagonist memantine on carrageenan-induced thermal hyperalgesia in rats. Eur J Pharmacol. 1994;255:123-129. 4.Neugebauer V, Kornhuber J, Lucke T, Schaible HG. The clinically available NMDA receptor antagonist memantine is antinociceptive on rat spinal neurones. Neuroreport. 1993;4:1259-1262. 5.Rabey JM, Nissipeanu R, Korczyn AD. Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease. J Neural Transm Park Dis Dement Sect. 1992;4:277-282. 6.Starck M, Albreacht H, Pollmann W, Straube A, Dieterich M. Drug therapy for acquired pendular nystagmus in multiple sclerosis. J Neurol. 1997;244:9-16.