Kinoshita K, Nagao T, Ono H
Pharmacological Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
Neuropharmacology. 1994 Oct;33(10):1183-8. doi: 10.1016/s0028-3908(05)80008-5.
Effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolinamide), a new thyrotropin releasing hormone (TRH) analog, on spinal reflex potentials and flexor reflexes were compared with those of TRH in C1-spinal rats. Intravenously administered TA-0910 and TRH produced dose-dependent increases in the amplitudes of mono- and polysynaptic reflex potentials and withdrawal flexor reflexes. TA-0910 was more potent and more long-lasting than TRH. The stimulating actions of TA-0910 and TRH on the monosynaptic reflex potential were not antagonized by pretreatment with atropine, cyproheptadine, haloperidol or prazosin, suggesting no involvement of the cholinergic, serotonergic, dopaminergic or noradrenergic system. Intraduodenally administered TA-0910 also produced a lasting potentiation of the withdrawal flexor reflex, but intraduodenally administered TRH showed no effect. These results suggest that TA-0910 may be a more useful drug than TRH for spinal functional disorders.
将新型促甲状腺激素释放激素(TRH)类似物TA-0910(1-甲基-(S)-4,5-二氢乳清酸-L-组氨酰-L-脯氨酰胺)与TRH对C1脊髓大鼠脊髓反射电位和屈肌反射的作用进行了比较。静脉注射TA-0910和TRH可使单突触和多突触反射电位以及退缩屈肌反射的幅度产生剂量依赖性增加。TA-0910比TRH更有效且作用更持久。TA-0910和TRH对单突触反射电位的刺激作用不会被阿托品、赛庚啶、氟哌啶醇或哌唑嗪预处理所拮抗,这表明胆碱能、5-羟色胺能、多巴胺能或去甲肾上腺素能系统未参与其中。十二指肠内注射TA-0910也会使退缩屈肌反射产生持久增强,但十二指肠内注射TRH则无作用。这些结果表明,对于脊髓功能障碍,TA-0910可能是比TRH更有用的药物。