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

To: Dr. John M. de Castro who wrote (654)	8/18/1999 5:07:00 PM
From: Dr. John M. de Castro	Read Replies (1) \| Respond to of 1494

Memantine is a safe & effective neuroprotectant in a neonatal stroke model. This suggests (with all the caution that must be exercised when generalizing from an animal model) that memantine may be effective in children as well as adults. This report is part of the ongoing research of Stuart Lipton whose research is in part underwriten by NTII. John de C Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. Stieg PE, Sathi S, Warach S, Le DA, Lipton SA, Eur J Pharmacol 1999 Jun 30;375(1-3):115-20 Excessive accumulation of glutamate or other excitatory amino acids and the subsequent overactivity of NMDA receptors is currently thought to lead to neuronal injury in cerebral ischemia. Therefore, antagonists of the NMDA receptor may offer an approach for the treatment of ischemic brain injury. Dizocilpine (MK-801), an NMDA receptor-associated channel blocker, protects neurons in several rodent stroke models. However, this drug has numerous side effects and causes apoptosis of neonatal neurons. Recently, another NMDA receptor-associated channel blocker, memantine, has been shown to ameliorate NMDA-receptor mediated neurotoxicity in neuronal cell cultures and in focal cerebral ischemia models in adult rats without substantial side effects. Memantine has been used clinically in the treatment of Parkinson's disease and spasticity for a number of years. Here we tested the effects of memantine on focal stroke caused by photochemical thrombosis in neonatal rats and demonstrated a neuroprotective effect of memantine in this model. We also found excellent correlation between infarct size determined by magnetic resonance imaging (MRI) and histopathological analysis in the same animals. A single pre-ischemic dose of memantine (20 mg/kg) given 15 min prior to induction of stroke reduced the infarct size by 36.3% when compared to control animals treated with normal saline (P < 0.0001). At this dosage, memantine manifests few, if any, neurobehavioral side effects. Thus memantine appears to be both safe and effective in neonatal as well as adult animal models of stroke.