Neuronal hyperexcitability and

In epilepsy certain neurons and/or groups of neurons become hyperexcitable and begin firing bursts of action potentials that propagate in a synchronous manner to other brain structures (and in the case of generalized seizures, to practically all areas of the brain). These may be the result of abnormalities in neuronal membrane stability or in the connections among neurons. It is known that the epileptic bursts consist of sodium-dependent action potentials and a calcium-dependent depolarizing potential. 

Mectianism of Action An anticonvulsant that blocks sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repef if ive neuronal firing, and diminishing synapfic impulses. Therapeutic Effect Prevenfs seizures. Pharmacokinetics Complefely absorbed from GI tract and extensively metabolized in the liver to active metabolite. Protein binding 40%. Primarily excreted in urine. Half-life 2 hr metabolite, 6-10 hr. 

It is a keto analog of carbamazepine. It produces blockade of voltage sensitive sodium channels, leading to stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing and diminution of propagation of synaptic impulses. 

Alcamprosate, a derivative of the amino acid taurine, interacts with the NMDA receptor and perhaps can substitute for this effect of alcohol during abstinence (Fig. 13-30). Thus, when alcohol is withdrawn and the mesolimbic D2 receptors are whining for dopamine because of too much glutamate, perhaps alcamprosate substitution will reduce the neuronal hyperexcitability of alcohol withdrawal, resulting... 

WilUngale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD (1997) Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 122 1593-1604 Willis WD Jr (1988) Dorsal horn neurophysiology of pain. Ann N Y Acad Sci 531 76-89 Willis WD, Westlund KN (1997) Neuroanatomy of the pain system and of the pathways that modulate pain. J CUn Neurophysiol 14 2-31... 

This meeting will focus on an emerging concept, that a multiplicity of molecularly and physiologically distinct Na channels contribute to neuronal hyperexcitability that can produce clinically significant signs and symptoms. This concept, and our meeting which will explore it, reflects the convergence of a number of important themes ... 

Sodium channels and neuronal hyperexcitability. Wiley, Chichester (Novartis Foundation Symposium 241) p 21SS... 

Bevan S 2002 Modulation of sodium channels in primary afferent neurons. In Sodium Channels and neuronal hyperexcitability. Wiley, Chichester (Novartis Found Symp 241) p 144—158 Baker MD, Wood JN 2001 Involvement of Na channels in pain pathways. Trends in... 

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