Electrophysiological and neurochemical investigations on the action of carbamazepine on the rat hippocampus.
Carbamazepine moderately depressed the input fiber volley resulting in attenuation of the dendritic epsp and the population spike in CA1 of rat hippocampal slices with a threshold concentration of 20 microM. The depressant effect on the population spike was not antagonized by the adenosine receptor blocker caffeine. Paired-pulse inhibition was not affected by carbamazepine (40 microM). Epileptic-like rhythmic discharge of CA1 neurons in medium containing low Ca2+/high Mg2+ was attenuated at even lower concentrations of carbamazepine (8 microM) indicating that there was also a postsynaptic site of action. Imipramine being significantly more potent than carbamazepine in the rabbit corneal test for local anaesthetic activity had no effect on the population spike (20 microM). In neurochemical studies, carbamazepine reduced the [22Na]- and [3H]L-glutamate efflux induced by potassium and veratridine from hippocampal slices with a threshold concentration of 10 microM. The drug (400 microM) failed to affect Na+-dependent binding of [3H]L-glutamate to hippocampal synaptic membranes. In conclusion, the present findings demonstrate pre- and postsynaptic depressant actions of carbamazepine in CAI of hippocampus.
Olpe
H R
HR
Baudry
M
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Jones
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RS
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology*; D003864:Depression, Chemical; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D012964:Sodium / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014316:Tritium
D000779:Anesthetics, Local; D005971:Glutamates; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014316:Tritium; D002220:Carbamazepine; D002110:Caffeine; D018698:Glutamic Acid; D012964:Sodium; D007099:Imipramine