Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog, (I): Effects on the central nervous system by oral administration.

Effects of orally administered TA-0910, a new thyrotropin-releasing hormone (TRH) analog, on the central nervous system (CNS) were investigated and compared with those of TRH. TA-0910 shortened the duration of pentobarbital-induced sleep and antagonized reserpine-induced hypothermia at 0.3 mg/kg or more in mice. TA-0910 enhanced the spontaneous motor activity at the higher dose of 30 mg/kg in mice. The drug also activated acute spontaneous EEGs in rabbits at 1 mg/kg. TRH produced these effects at about 100 times higher doses than TA-0910. In antagonizing pentobarbital-induced sleep, the dose ratios of i.v. versus p.o. of TA-0910 and TRH were about 1/10 and 1/100, respectively. The duration of the antagonistic action of TA-0910 on pentobarbital-induced sleep in mice was about 8 times longer than that of TRH when administered orally as well as intravenously. These potent and long-acting TA-0910 effects on the CNS are discussed in connection with its biotransformation.