Watanabe Arata, Nakai Akio, Tohyama Yoshihiro, Nguyen Khnah Q, Diksic Mirko
Cone Neurological Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
Nucl Med Biol. 2006 Apr;33(3):325-32. doi: 10.1016/j.nucmedbio.2005.08.002. Epub 2006 Mar 9.
Anpirtoline has been described as an agonist at 5-HT1B receptors with a relatively high potency. It also acts as an agonist at 5-HT1A receptors, but has a lower potency than at the 5-HT1B sites. There is very little known about the mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the present study was to investigate the effects of acutely and chronically administered anpirtoline on 5-HT synthesis in the rat brain using the autoradiographic alpha-[14C]methyl-L-tryptophan method. In the acute study, anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the tracer injection. The control rats were injected with the same volume of saline. In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously in saline once a day for 10 days. There were no significant differences between the plasma-free and total tryptophan concentrations between the anpirtoline treatment and the respective control groups. In the acute experiment, 5-HT synthesis rates in all of the brain areas investigated were significantly decreased by anpirtoline when compared to the saline-treated group. In the chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the projection areas, as well as the raphe nuclei, were normalized or had a tendency to be normalized. These results suggest that it is likely that the terminal 5-HT1B receptors are involved in the regulation of 5-HT synthesis in the projection areas and that 5-HT synthesis, in the raphe, is likely influenced by anpirtoline's 5-HT1A and/or 5-HT1B agonistic properties.
安匹托林被描述为一种对5-HT1B受体具有较高亲和力的激动剂。它也可作为5-HT1A受体的激动剂，但效力低于在5-HT1B位点。关于安匹托林影响局部5-羟色胺合成的机制知之甚少。本研究的目的是使用放射自显影α-[14C]甲基-L-色氨酸方法，研究急性和慢性给予安匹托林对大鼠脑内5-羟色胺合成的影响。在急性研究中，在注射示踪剂前30分钟腹腔注射安匹托林（2.0毫克/千克）。对照大鼠注射相同体积的生理盐水。在慢性研究中，每天皮下注射一次安匹托林（每天2毫克/千克），共10天。安匹托林治疗组和相应对照组之间的游离血浆和总色氨酸浓度没有显著差异。在急性实验中，与生理盐水处理组相比，安匹托林显著降低了所有研究脑区的5-羟色胺合成率。在慢性安匹托林实验中，几乎所有投射区以及中缝核的5-羟色胺合成率恢复正常或有恢复正常的趋势。这些结果表明，终末5-HT1B受体可能参与投射区5-羟色胺合成的调节，并且中缝核中的5-羟色胺合成可能受安匹托林的5-HT1A和/或5-HT1B激动特性影响。
