NS-3 (CG3703), an analog of thyrotropin-releasing hormone, ameliorates cognitive impairment in rats.

The effects of thyrotropin-releasing hormone (TRH) and its analog, N-[[(3R,6R)-6-methyl-5-oxo-thiomorpholinyl] carbonyl]-L-histidyl-L- prolinamide tetrahydrate (NS-3, CG3703) on disturbance of memory of a passive avoidance response (PAR) and an escape response in rats were investigated. NS-3 improved amnesia caused by scopolamine, electroconvulsive shock (ECS), and cycloheximide (CXM), but TRH improved only the ECS-induced amnesia. NS-3 reversed learning deficits caused by hypercapnia, but TRH had no effect. These differences in the effect between NS-3 and TRH may be due to their biological half-life in rat plasma. These results suggest that NS-3 possesses more potent antiamnestic effects than TRH in rats.