Effects of a new TRH analogue, YM-14673 on a passive avoidance test as a possible criterion of improvement in cognitive disturbance in rodents.

Effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on cognitive disturbance of passive avoidance response were studied in rodents in comparison with those of TRH and CDP-choline. The latency for entering from the illuminated into the dark compartments was shortened in anoxia and scopolamine-treated rats, cycloheximide-treated mice and cerebral ischemic gerbils. The shortened latency in these models was prolonged by administration of both YM-14673 and TRH in doses without effect on spontaneous movement. YM-14673 was about 10 times more potent than TRH in ameliorating the cognitive disturbance, whereas CDP-choline showed no influence on the learning ability. These results suggest that YM-14673 and TRH possess facilitatory effects on cerebral function and that YM-14673 was distinct from CDP-choline in pharmacological profile.