Neurochemical study of TA-0910, a new TRH analog

• Published in: Japanese Journal of Pharmacology 1992, Vol.58 (suppl.1), p.95-95
• Main Authors: Yumiko Shibutani, Kazutaka Kawashima, Isao Fukuchi, Michio Yamamura, Yuzo Matsuoka, Ryuichi Ishida
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Effects of TA-0910 and TRH on brain acetylcholine (ACh) metabolism were investigated in rats by measuring ACh levels in the cerebral cortex (CC), hippocampus (HI) and corpus striatum (ST) using HPLC-ECD. TA-0910 (3 and 10 mg/kg, i.p.) caused a dose-dependent decrease in ACh level in the HI but no significant influence in the CC and ST, whereas it decreased choline (Ch) levels in these 3 regions. On the other hand, TRH (30 mg/kg, i.p.) shoved no effect on ACh levels. It only produced a decrease in Ch level in the CC. In the CC and HI, TA-0910 inhibited the ACh accumulation induced by pentobarbital・Na (40 mg/kg, i.p.) at 0.3 and 1 mg/kg, i.v. and by γ-butyrolactone (GBL：1000 mg/kg, i.p.), a nerve impuls flow blocker, at 1,3 and 10 mg/kg, i.p. TRH inhibited the ACh accumulation induced by pentobarbital in the CC and HI at 3 and 10 mg/kg, i.v. and by GBL in the HI at 30 mg/kg, i.p. TA-0910 (1, 3 and 10 mg/kg, i.p.) accelerated the ACh accumulation rate in the CC and HI after physostigmine (1 mg/kg, i.p.) treatment, whereas TRR (30 mg/kg, i.p.) caused no significant influence. These results suggest that TA-0910 facilitates ACh turnover rate in rat brain.