Epilepsy neuroprotection

GABA GABAa Rat brain Alcoholism, CNS, anesthesia, epilepsy, anxiety, depression, Parkinson s disease, pain, migraine, respiratory gastrointestinal, diabetes, obesity Synaptic inhibition, decrease in neuronal excitability increase in cellular chloride influx, neuroprotection, sedation/hypnosis, anticonvulsant activity muscle relaxation... 

Na+ channel Site 2 Rat brain Cardiac arrhythmia, epilepsy, Alzheimer s disease, pain, gastrointestinal, stroke, glaucoma Control of neuronal and cardiac electrical activity, neuroprotection... 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

Since the early 1980s, much effort has focused on animal models of acute and chronic neurodegeneration in search of therapeutics for stroke. Neuronal cell death follows strokes, acute ischemic insults, and chronic neurodegeneration, such as Parkinson s disease, Alzheimer s disease (AD), epilepsy, and Huntington s disease. Up to 80% of all strokes result from focal infarcts and ischemia in the middle cerebral artery (MCA), so the commonly used animal models for neuroprotection are produced by temporary or permanent occlusion of the MCA.5 Lesions of the MCA include occlusion by electrocoagulation, intraluminal monofilaments, photochemical effects, thrombosis, and endothelin-1, but all of these models necessitate studying reperfusion events and validating MCA occlusion by behavioral assessments. 

Safinamide is a mixed Na+ and Ca2+ channel blocker with anticonvulsant, neuroprotective and anti-parkinsonian properties and is currently in phase II clincical trials for the indications epilepsy and Morbus parkinson (for review see Chazot, 2001). Additionally, analgesic activity has been shown in acute pain models (hot plate, tail flick) and more pronounced in a chronic, persistent pain model (formalin test) in mice in a dose range of 7.5 to 120 mg/kg p.o. (Salvati et al., 1999). 

Urbanska, E.M., Czuczwar, S.J., Kleinrok, Z., Turski, W.A. (1998). Excitatory amino acids in epilepsy glutamate, neurodegeneration and neuroprotection more pieces in the puzzle. Restor. Neurol. Neurosci. 13 85-115. 

Treatment during or after brain injury in chronic epilepsy models, such as SE and kindling, reduce cell loss and neuronal death. Such neuroprotection could contribute to modification of or delay in the development of epilepsy. 

The definition of an antiepileptogenic compound is one that prevents or slows the process of developing epilepsy (Cole and Dichter, 2002). Several experimental studies have aimed at preventing epileptogenesis in animal models, including SE and kindling models, by administering AEDs. Some have mild or questionable effects, and others are without effect even if they neuroprotect (Walker et al., 2002). 

Arzimanoglou, A, Hirsch, E, Nehlig, A, Castelnau, P, Gressens, P, Pereira de Vasconcelos, A (2002) Epilepsy and neuroprotection an illustrated review. Epileptic Disord, 4 173-182. 

Rigoulot, MA, Koning, E, Ferrandon, A, Nehlig, A (2004) Neuroprotective properties of topiram-ate in the Uthium-pilocarpine model of epilepsy. J Pharmacol Exp Ther, 308 787-795. 

Perin-Dureau F, RachUne J, Neyton J, Paoletti P (2002) Mapping the binding site of the neuroprotectant ifenprodU on NMDA receptors. J Neurosd 22 5955-5965 Rogawski MA (1992) The NMDA receptor, NMDA antagonists and epilepsy therapy. A status report. Drugs 44 279-292... 

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