Anticonvulsant action of the nucleoside transport inhibitor, soluflazine, on synaptic and non-synaptic epileptogenesis in the guinea-pig hippocampus

doi:10.1016/0920-1211(88)90021-6

Epilepsy Research

Volume 2, Issue 2, March–April 1988, Pages 65-71

https://doi.org/10.1016/0920-1211(88)90021-6 Get rights and content

Abstract

The effects of the nucleoside transport inhibitor, soluflazine, were examined on synaptic and non-synaptic epileptogenesis, and on paired-pulse facilitation and inhibition in the CA1 region of the guinea-pig hippocampal slice. In the model of synaptic epileptogenesis, excitation was enhanced by omitting Mg²⁺ from the artificial cerebrospinal fluid (ACSF). This procedure induced a second epileptogenic population spike (PS) after orthodromic stimulation, which was inhibited by soluflazine (IC₅₀ value 1.2 × 10⁻⁶ M). In the nonsynaptic model of epileptogenesis spontaneous depolarizing ‘burst’ discharges were induced in CA1 by lowering the concentration of Ca²⁺ and increasing the concentration of K⁺ and Mg²⁺. The IC₅₀ value of soluflazine was 6.0 × 10⁻⁷ M for antagonizing ‘burst’ frequency and 7.5 × 10⁻⁶ M for ‘burst’ amplitude, indicating a preferential effect on ‘burst’ initiation. After paired orthodromic stimuli to stratum radiatum, the amount of synaptic facilitation of PS amplitude was significantly increased by soluflazine. This was mainly due to a decrease in the size of the PS induced by the conditioning pulse. The amount of PS inhibition after antidromic/orthodromic stimulation was not significantly altered by soluflazine. With the exception of the failure of soluflazine to attenuate inhibition, the results obtained with soluflazine resemble those reported for adenosine. This strengthens the hypothesis that soluflazine increases the extracellular concentration of adenosine. Further, the results indicate that centrally active nucleoside transport inhibitors may be a new class of antiepileptic drug.

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Research reportAnticonvulsant action of the nucleoside transport inhibitor, soluflazine, on synaptic and non-synaptic epileptogenesis in the guinea-pig hippocampus

Abstract

Eur. J. Pharmacol.

Neurosci. Biobehav. Rev.

Neurosci. Lett.

Brain Res.

Brain Res.

Exp. Neurol.

Brain Res.

J. Biol. Chem.

Comparative action of flunarizine, phenytoin and two calcium-entry blockers on spontaneous bursts in the low calcium hippocampal slice preparation

Drug Dev. Res.

Field-potential assay of anticonvulsant drugs in the hippocampal slice

Epilepsia

Adenosine inhibits epileptiform activity arising in hippocampal area CA3

Br. J. Pharmacol.

Regulatory effects of neurotransmitters on electroshock and pentylenetetrazol seizures

Research report
Anticonvulsant action of the nucleoside transport inhibitor, soluflazine, on synaptic and non-synaptic epileptogenesis in the guinea-pig hippocampus