Ameri A, Seitz U
Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
Exp Brain Res. 1998 Aug;121(4):451-6. doi: 10.1007/s002210050480.
Mesaconitine, one of the main alkaloids contained in Aconiti tubers, is a centrally acting analgesic without affinity to opioid receptors. It has been reported that the antinociception is due to an interaction with the noradrenergic system. In the present study, the effect of mesaconitine on the uptake of noradrenaline and on neuronal activity was examined in rat hippocampus. Experiments were performed as a study of [3H]noradrenaline uptake into rat hippocampal synaptosomes. Mesoconitine inhibited [3H]noradrenaline uptake in a concentration-dependent manner with a Ki of 111.95+/-18 nM. In a further series of experiments, the effects of mesaconitine on the extracellularly recorded population spike were investigated in rat hippocampal slices. At a concentration of 10 nM, mesaconitine increased the amplitude of the postsynaptic population spike by 31.10%+/-6.7% of control and elicited one or two additional spikes. The presynaptic fiber spike and the field excitatory postsynaptic potential were not affected by this alkaloid. The enhancement of neuronal activity was abolished by 1 microM propranolol as well as by 1 microM timolol. It is concluded that mesoconitine increased the excitability in rat hippocampal pyramidal cells by an involvement of the noradrenergic system, with at least one mechanism being inhibition of noradrenaline uptake leading to an enhanced extraneuronal noradrenaline level.
中乌头碱是乌头块根中含有的主要生物碱之一，是一种中枢性镇痛药，对阿片受体无亲和力。据报道，其镇痛作用是由于与去甲肾上腺素能系统相互作用所致。在本研究中，检测了中乌头碱对大鼠海马体中去甲肾上腺素摄取及神经元活性的影响。实验采用研究[3H]去甲肾上腺素摄取到大鼠海马体突触体中的方法进行。中乌头碱以浓度依赖性方式抑制[3H]去甲肾上腺素摄取，其Ki值为111.95±18 nM。在另一系列实验中，研究了中乌头碱对大鼠海马体切片细胞外记录的群体峰电位的影响。在浓度为10 nM时，中乌头碱使突触后群体峰电位的幅度增加了对照值的31.10%±6.7%，并引发了一两个额外的峰电位。该生物碱对突触前纤维峰电位和场兴奋性突触后电位无影响。1 μM普萘洛尔和1 μM噻吗洛尔均可消除神经元活性的增强。结论是，中乌头碱通过去甲肾上腺素能系统参与增加大鼠海马体锥体细胞的兴奋性，至少有一种机制是抑制去甲肾上腺素摄取导致细胞外去甲肾上腺素水平升高。
