Protective effects of TRH and its analogues in chemical and genetic models of seizures.

TRH shows strong influence on neuronal excitability and may participate in the regulation of seizures. We investigated the effect of TRH and its stable analogues on seizures induced by intravenous (i.v.) infusion of pentetrazole in rats. The data showed that i.v. administration of TRH (10 and 20 mg/kg), RGH-2202 (0.1 mg/kg) and Z-p-Glu-His-Pro-NH2 (10 mg/kg) increased threshold for pentetrazole-induced clonic seizures, but did not affect the tonic ones. Another stable analogue of TRH, 1p-Glu-Tyr-Pro-NH2 (0.1-10 mg/kg), had no effect on pentetrazole-induced seizures. In further study, effects of TRH and RGH-2202 were examined in WAG/Rij rats, a genetic model of absence epilepsy. TRH (25 and 50 micrograms i.c.v.) decreased dose-dependently the number and mean duration of spike-wave discharges in cortical EEG of WAG/Rij rats at 90 and 120 min after the peptide administration. On the other hand, RGH-2202 (1 microgram i.c.v.) significantly decreased only the number of spike-wave discharges at 60 min post-injection. These results confirm that TRH and some of its analogues have moderate antiepileptic activity.