Nagai Y, Narumi S, Saji Y, Nagawa Y
Nihon Yakurigaku Zasshi. 1985 Apr;85(4):221-30. doi: 10.1254/fpj.85.221.
The antagonistic effect of a TRH (Thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate) against reserpine-induced reduction of electroconvulsive threshold (EC50) and the involvement of monoaminergic mechanism were studied in mice. Reserpine (2 mg/kg, i.p.) reduced the EC50 to 55-77% of the control in association with the depletion of brain monoamine. TRH and DN-1417 significantly reversed the EC50 reduced by reserpine. DN-1417 partially recovered 5-HT level and increased in the brain levels of 3-methoxy-4-hydroxyphenylglycol, homovanillic acid and 5-hydroxyindoleacetic acid in reserpinized mice. Monoaminergic receptor blockers attenuated, but muscarinic blockers accelerated the antagonistic effects of DN-1417 on the EC50. Neither alpha-methyl-p-tyrosine nor FLA-63 inhibited the effects of DN-1417, whereas p-chlorophenylalanine not only inhibited the antagonistic effect of DN-1417 on the EC50 but also prevented the stimulation effect on 5-HT turnover. Therefore, the antagonistic effect of DN-1417 against reserpine on the EC50 is most likely mediated by the stimulation of monoamine turnover, especially 5-HT in mice.
在小鼠中研究了促甲状腺激素释放激素（TRH）类似物DN - 1417（γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺柠檬酸盐）对利血平诱导的电惊厥阈值（EC50）降低的拮抗作用以及单胺能机制的参与情况。利血平（2mg/kg，腹腔注射）使EC50降低至对照的55 - 77%，同时伴有脑单胺耗竭。TRH和DN - 1417显著逆转了利血平降低的EC50。DN - 1417部分恢复了利血平化小鼠的5-羟色胺水平，并提高了脑内3-甲氧基-4-羟基苯乙二醇、高香草酸和5-羟基吲哚乙酸的水平。单胺能受体阻滞剂减弱了DN - 1417对EC50的拮抗作用，但毒蕈碱受体阻滞剂加速了这种作用。α-甲基-对-酪氨酸和FLA - 63均未抑制DN - 1417的作用，而对氯苯丙氨酸不仅抑制了DN - 1417对EC50的拮抗作用，还阻止了其对5-羟色胺周转的刺激作用。因此，DN - 1417对利血平在EC50上的拮抗作用很可能是通过刺激单胺周转，尤其是小鼠体内的5-羟色胺来介导的。
