Ameri A
Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jun;357(6):585-92. doi: 10.1007/pl00005212.
In the present study the effects of the two Aconitum alkaloids 14-benzoyltalitasamine and talitasamine on neuronal activity were investigated in order to obtain further insight into structure-dependent effects of this group of alkaloids on central nervous activity. Both alkaloids are closely related to aconitine, the main alkaloid of plants of Aconitum species. However, they have shortened side chains at position C3 and C8 of the molecule. The experiments were performed as extracellular recordings of orthodromically and antidromically evoked population spikes as well as of field excitatory potentials (EPSPs) from the CA1 region of rat hippocampal slices. 14-Benzoyltalitasamine exerted a reversible inhibition of the field potentials in a concentration-dependent manner. The orthodromic population spike was attenuated at concentrations higher than 1 microM, while the field EPSP was already affected at a concentration of at least 0.3 microM. Both responses were completely blocked at a concentration of 30 microM. The alkaloid failed to affect the presynaptic fiber spike at concentrations less than 10 microM. There was only a up to 30% decrease in the antidromic population spike (10-100 microM). The inhibition of the antidromic spike was increased by using a higher stimulus frequency. In contrast to 14-benzoyltalitasamine, the alkaloid talitasamine which is lacking the benzoylester side chain was a less effective inhibitor of the orthodromic population spike and even failed to affect the antidromic spike. Furthermore, the effects of the alkaloids on experimentally induced epileptiform activity was examined. While talitasamine was lacking any significant effect at concentrations less than 100 microM, 14-benzoyltalitasamine reversibly reduced both stimulus-triggered epileptiform activity in area CA1 elicited by omission of Mg2+ from the bathing medium as well as spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg2+ and elevation of K+ to 5 or 8 mM. The antiepileptiform efficacy of this compound was concentration-dependent (0.3-10 microM) and manifested itself as a decrease in burst frequency as well as in burst amplitude and was significantly increased by the higher K+ concentration.
在本研究中，对两种乌头生物碱14-苯甲酰塔拉他敏和塔拉他敏对神经元活性的影响进行了研究，以便进一步深入了解这类生物碱对中枢神经活性的结构依赖性作用。这两种生物碱都与乌头属植物的主要生物碱乌头碱密切相关。然而，它们在分子的C3和C8位具有缩短的侧链。实验采用细胞外记录法，记录大鼠海马切片CA1区顺向和逆向诱发的群体锋电位以及场兴奋性突触后电位（EPSP）。14-苯甲酰塔拉他敏以浓度依赖性方式对场电位产生可逆性抑制。当浓度高于1μM时，顺向群体锋电位减弱，而场EPSP在浓度至少为0.3μM时就已受到影响。在浓度为30μM时，两种反应均被完全阻断。该生物碱在浓度低于10μM时对突触前纤维锋电位无影响。逆向群体锋电位仅在浓度为10 - 100μM时有高达30%的降低。通过使用更高的刺激频率可增强对逆向锋电位的抑制作用。与14-苯甲酰塔拉他敏不同，缺乏苯甲酰酯侧链的生物碱塔拉他敏对顺向群体锋电位的抑制作用较弱，甚至对逆向锋电位无影响。此外，还研究了这些生物碱对实验性诱发的癫痫样活动的影响。当浓度低于100μM时，塔拉他敏无明显作用，而14-苯甲酰塔拉他敏可可逆性降低通过从浴液中去除Mg²⁺在CA1区诱发的刺激触发癫痫样活动以及通过去除Mg²⁺并将K⁺浓度升高至5或8 mM在CA3区自发出现的癫痫样活动。该化合物的抗癫痫样作用具有浓度依赖性（0.3 - 10μM），表现为爆发频率以及爆发幅度降低，并且在较高的K⁺浓度下显著增强。
