[Anticonvulsant effects of TRH analog. 3. Prophylactive effects of DN-1417 on kindling model]

We reported previously that TRH . T and a novel TRH analog, DN-1417 had anticonvulsant effects in kindling cat preparations which had been established as an experimental model of epilepsy. Although acute anticonvulsant effect of DN-1417 was short-lasting without dose-related efficacy, DN-1417 administration resulted a lasting increase in convulsive threshold in some cases. In order to study the effects of DN-1417 on kindling seizure development (prophylactic effect), 10 amygdaloid kindling cats were examined. The animals in the DN-1417 group (N = 4) were treated with the agent (1 mg/kg) prior to each daily kindling stimulation for 35 days (drug sessions). Six cats in control group were kindled without drug treatment. Kindling rates, changes in after-discharge duration, and positivity of transference phenomenon to contralateral amygdala were compared between these two groups. The results obtained were: 1) Positive prophylactic effects on kindling was found in 3 cats of DN-1417 group. In these cats, 19 (7-37) additional daily stimulation to those given during the drug session were required for the kindling. 2) No positive transfer to contralateral amygdala was found in 2 of 3 cats of DN-1417 group. 3) During the drug sessions, self-sustained afterdischarges were fragmented into separated bursts of discharges with short duration in 2 cats of DN-1417 group. These results suggested that DN-1417 may prevent a trans-synaptic change underlying the kindling, which might relate to the long-lasting anticonvulsant effect reported clinically. A possible mechanism underlying the prophylactic effects of DN-1417 was discussed.(ABSTRACT TRUNCATED AT 250 WORDS)