This study compared levetiracetam (Keppra) with reference antiepileptic drugs (AEDs) in the rat pilocarpine model of temporal lobe epilepsy. Electroencephalogram (EEG) recordings showed that i.p. administration of valproate (300 mg/kg), phenobarbital (5 mg/kg) and clonazepam (0.5 mg/kg) all significantly delayed the appearance of the first epileptic spike discharge in hippocampus as well as synchronous epileptiform activity in hippocampus and cortex. In contrast, i.p. administration of levetiracetam (17 mg/kg) only significantly delayed the appearance of the latter. This was corroborated by findings showing that i.p. administration of levetiracetam (17 mg/kg) significantly opposed pilocarpine-induced increases in the amplitude of the orthodromic population spike in the hippocampal CA3 area of urethane-anaesthetised rats, while valproate (200 mg/kg), phenobarbital (10 mg/kg) and clonazepam (1 mg/kg) had no effect. Pre-treatment i.p. with phenobarbital (10 mg/kg) and clonazepam (0.5 mg/kg) significantly reversed seizure-induced changes in aspartate and GABA concentrations while valproate (300 mg/kg) significantly reduced aspartate concentrations further. In contrast, levetiracetam (34 mg/kg) significantly counteracted all seizure-induced alterations in amino acid concentrations. Midazolam induced significant seizure protection after microinjection into substantia nigra pars reticulata (SNR, 50 nmol), nucleus accumbens (NA, 25 nmol) and caudate putamen (CP, 25 nmol), whereas phenytoin (50 nmol) only showed significant seizure protection after injection into the latter area. Levetiracetam differed by significant seizure protection after injection into SNR (1,000 nmol) and NA (3,000 nmol). These results suggest that levetiracetam is distinct from other AEDs by its ability to selectively suppress synchronisation of neuronal spike and burst firing in hippocampus.

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A novel interpretation of the existing data concerning the energy changes associated with nerve impulse propagation is proposed. The main conclusion is that the negative phase of the initial heat of activity cannot be accounted for without recourse to conformational changes in membrane proteins. It stems from analyzing and computing the energy changes associated with ionic flows, capacitive currents, and structural changes in membrane gateways. A close quantitative agreement with microcalorimetric measurements was achieved.Since the now classical measurements of heat production in nerve by A. V. Hill, it is a well-established fact that the energy changes associated with nerve activity can be divided into two phases: (i) an initial heat of activity, and (ii) heat production associated with the recovery processes.The initial heat of activity expresses the external dissipation of free internal energy due to the specific processes occurring in the nerve fiber during the action potential (AP) (1, 2). In the apparent order of their appearance, these processes are:(i) structural changes in the membrane as a result of the biochemical events in the membrane proteins induced by the changes in the electrical field;(ii) redistribution of electric charges in the membrane, phenomenologically termed the capacitive current (Ic) which expresses at the microscopic (molecular) level both the redistribution of electrons on the membrane lipids (the "dielectric" of the membrane capacity) and the intramembranous currents associated with the actuation of the gateways; and (Mi) ionic flows through specific channels (gateways), obviously implying ionic interchanges between the axoplasm and the interstitial fluid. Besides these three types of events there is a reversible ionic exchange of Ca2+ for K+ between the axoplasm and the membrane, extensively discussed by Tasaki (3). These Ca2+ movements have been discussed by others (4) in terms of early and late Ca2+ currents. The contribution of these events to the thermal changes appears to be of the order of a few percent (see below).Owing to the authoritative domination of the ionic theory, only processes ii and iii have been considered, under various names such as condenser theory, local circuit heat, and ionic mixing and interchange (5-7). The energetics of structural changes occurring in the membrane itself have been practically neglected. On the basis of a rough approximation, Ritchie (6) rejected acetylcholene (AcCh) hydrolysis as an explanation for the residual (net) heat, but this cannot restrain further investigations of molecular correlates of the initial heat of activity. An attempt by Wei (8) to ascribe the heat production and absorption in the nerve axon to the displacement of dipoles in the electric field would imply the association of all the energyThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. c...