The present work was designed to examine the effect of isoteoline on neuronal excitability in mice. Isoteoline has previously been shown to behave as a S-HT2 antagonist in a number of experimental settings with results indicating possible selectivity of the compound for 5-HT2C receptors. These serotonergic receptors are implicated, amongst many other functions, in modulating seizure susceptibility. Mutant mice lacking 5-HT2C receptors have been shown to suffer spontaneous seizures and higher mortality. This has lead to the notion that serotonin may be involved in the pathogenesis of epilepsy. However, no 5-HT2 antagonist has sofar been shown to possess pro-convulsive activity. We used the model of pentylnetetrazole (PTZ)-induced seizures to assess the anticonvulsive effect of the 5-HT2C agonist chlorophenylpiperazine (mCPP). It proved to prevent significantly the clonic and tonic seizures induced by a sub-maximal dose of PTZ. 1ST which was expected if anything to act pro-convulsively was tested against PTZ at a dose equal to its ED50. No such effect was observed; on the contrary, a slight insignificant anticonvulsive tendency was noted. On the other hand, IST tended to antagonize the anticonvulsive effect of mCPP, but the effect failed to reach statistical significance. The results are discussed in the light of similar data from the literature concerning 5-HT2C antagonists. In addition, the failure of 1ST to significantly antagonize the protective effect of mCPP is sought to be explained, possibly by its dopaminomimetic activity.
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