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.
Yamamura
M
M
Department of Pharmacology, Tanabe Seiyaku, Osaka, Japan.
Kinoshita
K
K
Nakagawa
H
H
Tanaka
T
T
Maeda
K
K
Ishida
R
R
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004569:Electroencephalography; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; D010424:Pentobarbital