Lamotrigine (LAG) is a new antiepileptic drug which is licensed as adjunctive therapy for partial and secondary generalized seizures. In the present study, the mechanisms responsible for its antiepileptic effect were studied in rat amygdaloid slices using intracellular recording and whole-cell patch clamp techniques. Bath application of LAG (50 microM) reversibly suppressed the excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) evoked by stimulating ventral endopyriform nucleus. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptor (EPSPNMDA) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,10 microM) and gamma-aminobutyric acidA receptor antagonist bicuculline (20 microM). LAG produced a parallel inhibition of EPSPNMDA. Postsynaptic depolarization induced by alpha-amino-5-methyl-4-isoxazole propionate (AMPA) was not altered by LAG. In addition, LAG increased the ratio of the second pulse response to the first pulse response (P2/P1), which is consistent with a presynaptic mode of action. The L-type Ca+2 channel blocker nifedipine (20 microM) had no effect on LAG-induced presynaptic inhibition. However, the depressant effect of LAG was markedly reduced in slices pretreated with N-type Ca+2 channel blocker omega-conotoxin-GVIA (omega-CgTX-GVIA, 1 microM) or a broad spectrum Ca+2 channel blocker omega-conotoxin-MVIIC (omega-CgTX-MVIIC, 1 microM). It is concluded that a reduction in omega-CgTX-GVIA-sensitive Ca+2 currents largely contributes to LAG-induced presynaptic inhibition.

1 Topiramate is a structurally novel anticonvulsant which was recently approved for adjunctive therapy in partial and secondarily generalized seizures. The present study was aimed at elucidating the mechanisms underlying the anticonvulsant e cacy of topiramate using intra-and extracellular recording techniques in the in vitro hippocampal slices. 2 When stimuli were delivered every 20 s, topiramate had no measurable e ect on both ®eld excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs). However, increasing the stimulation frequency from 0.05 ± 0.2 Hz, topiramate signi®cantly decreased the slope of fEPSP and the amplitude of PS in a concentration-dependent manner. The amplitude of presynaptic ®ber volley was also reduced. 3 Topiramate did not a ect the magnitude of paired-pulse inhibition and monosynaptically evoked inhibitory postsynaptic potentials (IPSPs). 4 Sustained repetitive ®ring was elicited by injection of long duration (500 ms) depolarizing current pulses (500 ± 800 pA). Superfusion with topiramate signi®cantly reduced the number of action potentials evoked by a given current pulse. 5 After blockade of GABA receptors by bicuculline, burst ®ring which consisted of a train of several spikes riding on a large depolarizing wave termed paroxysmal depolarizing shift (PDS) was recorded. Application of topiramate reduced the duration of PDS and later spikes with less e ect on the initial action potential. 6 These results suggest that frequency-dependent inhibition of neuronal activity due to blockade of Na + channels may account largely for the anticonvulsant e cacy of topiramate.

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Phenytoin is a commonly prescribed antiepileptic drug. Due to its saturation (zero-order) pharmacokinetics, phenytoin carries a special risk of dose-related toxicity that is an important issue in emergency medicine. The purpose of this cross-sectional case-series study was to investigate the causes, symptoms, misdiagnoses, and outcomes of acute phenytoin intoxication. It was based on a retrospective chart review of 30 inpatients (mean age, 41.6 +/- 22.8 years) with 36 episodes of acute phenytoin intoxication at our university hospital in the past 13 years. The average initial serum phenytoin level was 47.3 +/- 9.7 microg/mL (range, 27.9-70.4 microg/mL). Excessive self-medication, misunderstanding of the prescription order, and probable drug interaction were the three leading causes of acute phenytoin intoxication. Unsteady gait, dizziness/vertigo, nausea/vomiting, general weakness, and drowsiness were the most common presenting symptoms. The tentative diagnostic accuracy was 67%. The most common initial misdiagnosis was brainstem or cerebellum stroke (14%). The clinical course in all patients was uneventful under temporary withdrawal of phenytoin and supportive care. We concluded that acute phenytoin intoxication was relatively under-diagnosed in the emergency service. Although acute phenytoin intoxication causes no mortality and has a good outcome, the unsteady gait increases the risk of injuries caused by falls. The management of acute phenytoin intoxication includes temporary withdrawal of phenytoin and supportive care.

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