Wakabayashi H, Shimada K, Satoh T
Department of Analytical Chemistry, Niigata College of Pharmacy, Japan.
Chem Pharm Bull (Tokyo). 1991 Oct;39(10):2674-6. doi: 10.1248/cpb.39.2674.
The effect of diazepam (DZP) on melatonin synthesis in rat pineal gland was investigated in vivo. Subcutaneous injection of DZP (3 mg/kg) 1 h before the start of darkness significantly suppressed nocturnal elevations of pineal N-acetylserotonin (NAS) and melatonin contents in rats, and caused a 2-h delay in reaching the maximum melatonin level in the dark phase. DZP treatment also markedly suppressed the dark-induced increase of pineal N-acetyltransferase activity, which catalyzes the rate-limiting step in melatonin synthesis, but had no effect on hydroxyindole-O-methyltransferase activity, which catalyzes the final step of melatonin formation. Pineal norepinephrine and dopamine contents, in contrast, were not altered by DZP injection. The distribution rate of DZP to the brain reached the highest level 30 min after a single injection, while that to the pineal gland was observed 5 h later (i.e., 4 h after the start of darkness). It is clear that the inhibitory effect of DZP on melatonin synthesis in rat pineal gland appears concomitantly with the increase in the distribution volume of DZP into this gland. These results suggest that the inhibitory effect of DZP on melatonin synthesis results from the drug's direct action on the rat pineal gland.
在体内研究了地西泮（DZP）对大鼠松果体褪黑素合成的影响。在黑暗开始前1小时皮下注射DZP（3mg/kg）可显著抑制大鼠松果体N-乙酰血清素（NAS）和褪黑素含量的夜间升高，并使黑暗期达到最大褪黑素水平的时间延迟2小时。DZP处理还显著抑制了黑暗诱导的松果体N-乙酰转移酶活性的增加，该酶催化褪黑素合成中的限速步骤，但对催化褪黑素形成最后一步的羟基吲哚-O-甲基转移酶活性没有影响。相比之下，DZP注射并未改变松果体去甲肾上腺素和多巴胺的含量。单次注射后，DZP在脑中的分布率在30分钟时达到最高水平，而在松果体中的分布率在5小时后（即黑暗开始后4小时）观察到。很明显，DZP对大鼠松果体褪黑素合成的抑制作用与DZP在该腺体中分布容积的增加同时出现。这些结果表明，DZP对褪黑素合成的抑制作用是该药物对大鼠松果体的直接作用所致。
