Shimizu M, Yamamoto M, Kobayashi M
Department of Pharmacology, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Arch Int Pharmacodyn Ther. 1989 Sep-Oct;301:100-11.
The effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on spontaneous motor activity (SMA) were compared with those of TRH in rats. Intraperitoneal, oral and intracerebral administrations of YM-14673 caused a significant and dose-dependent increase in SMA. TRH also showed similar actions as YM-14673 did, except after oral dosing. These actions of YM-14673 were about 20-100 times more potent than those of TRH. Pretreatment with haloperidol, alpha-methyl-p-tyrosine (alpha-MT) and amino-oxyacetic acid (AOAA) but not atropine, inhibited the ability of both YM-14673 and TRH to increase SMA. Focal microinjection into the nucleus accumbens of both YM-14673 and TRH induced about 100 times more potent increases in SMA than similar injections into the dorsal striatum. It is suggested that YM-14673 possesses more potent facilitatory effects on SMA than TRH, and that these appear to be mediated mainly by the mesolimbic dopaminergic system rather than by the nigrostriatal one. Other possible mechanisms are also discussed.
将一种新型促甲状腺激素释放激素（TRH）类似物YM-14673（Nα-[[(S)-4-氧代-2-氮杂环丁烷基]羰基]-L-组氨酰-L-脯氨酰胺二水合物）对大鼠自发运动活性（SMA）的影响与TRH的影响进行了比较。腹腔注射、口服和脑内注射YM-14673均导致SMA显著且呈剂量依赖性增加。TRH除口服给药后外，也表现出与YM-14673类似的作用。YM-14673的这些作用比TRH强约20 - 100倍。用氟哌啶醇、α-甲基对酪氨酸（α-MT）和氨基氧乙酸（AOAA）预处理可抑制YM-14673和TRH增加SMA的能力，但阿托品预处理则无此作用。向伏隔核局部微量注射YM-14673和TRH所诱导的SMA增加比向背侧纹状体进行类似注射强约100倍。提示YM-14673对SMA的促进作用比TRH更强，且这些作用似乎主要由中脑边缘多巴胺能系统介导，而非黑质纹状体系统。还讨论了其他可能的机制。
