The prophylactic and anticonvulsant effects of a TRH analog (DN-1417) on amygdaloid kindling model of epilepsy.

Thyrotropin-releasing hormone (TRH) is a neuropeptide that is widely distributed throughout the CNS in addition to the hypothalamus and has a variety of CNS actions unrelated to its endocrine action via the pituitary-thyroid axis. A TRH analog, y -butyrolactone-y -carbanyl-L-histidyl-L-prolinamide citrate (DN-1417), has been reported3 to have a more profound CNS action with a Iess TSH-releasing activity than TRHtartrate (TRH-T). Recently, a therapeutic effect of DN14 17 on myoclonus epilepsy and Lennox syndrome has been reported.2 Our previous study showed that an intravenous administration of TRH-T and DN1417 has a short-lived anticonvulsant effect on kindled amygdaloid (AM) seizures in cats, although the effect had considerable individual variations and no dose-related responses.s A short-lived effect without doserelated responses appears to depend upon the degradation or less penetration through BBB after a systemic administration. In this study, we examined the prophylactic and anticonvulsant effects of intracerebroventricularly (ICV) administered DN-1417 on the AM kindling model of rats. Male Sprague-Dawley (SD) rats were ~~