EFFECTS OF NS-3, AN ANALOG OF THYROTROPIN-RELEASING-HORMONE, ON THE CENTRAL-NERVOUS-SYSTEM

The central nervous system (CNS) effects of thyrotropin-releasing hormone (TRH) and of its analogue, (3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-prolinamide tetrahydrate (NS-3, CG-3703) on the CNS were compared in mice and rats. NS-3 and TRH increased the spontaneous locomotor activity, reversed reserpine-induced hypothermia, antagonized narcosis caused by pentobarbital Na and protected mice from loss of consciousness caused by head concussion. The stimulatory effects of NS-3 on the CNS were 30 to 100 times more potent than those of TRH, although binding affinity of NS-3 to the TRH receptor was about 0.4 times that of TRH. TSH-releasing activity of NS-3 was 1.9 times more potent than that of TRH, but relative potency of NS-3 in CNS stimulatory activity was 15 to 50 times of that of TRH. NS-3 is more potent and has a longer duration of action than TRH because of its greater biological stability.