Durlach J, Rinjard P, Sprince H, Smith G G
Cons. d'Endocrinol. et Mal. Métabol., CHU Cochin Port Royal, Paris, France.
Methods Find Exp Clin Pharmacol. 1988 Jul;10(7):437-47.
Among several taurine derivatives, Ca N-acetylhomotaurinate (Ca AOTA) appears to be the most active anti-acetaldehyde and anti-alcohol agent. Studies of the antagonism of the hypomotility induced by high intravenous doses of acetaldehyde or ethanol in mice and of the lethality of high intragastric doses of acetaldehyde in rats show its superiority which appears logical after systematic studies of these derivatives and their components. The reinforcing action of the nervous activity due to N-acetylation of these sulfonic aminoacids differs according to the target. Since Ca AOTA is the most active against acetaldehyde and ethanol toxicity, this central nervous action first relies on its effects on neuromodulators, neuromediators and cations primarily involved in the mechanisms of alcohol dependence through its taurine (TA) structure, its gamma-aminobutyric acid (GABA) agonist actions, its anti-opioid receptor "naloxone-like" effects and its possible activity as a subcellular Ca carrier. Ca AOTA may also intervene through its high membrane stabilizing effect. Compared with the other compounds, it appears to be the most active both in vitro on the erythrocyte membrane of the rabbit and on the human amnion membrane and ex vivo on the alcoholic rat's erythrocyte membrane. Among several taurine derivatives similarly efficient in toxicity of both acetaldehyde and ethanol, Ca AOTA is the best. Its efficiency against the most toxic metabolite of ethanol may specifically rely on Ca and TA dependence of acetaldehyde-dehydrogenase or on an aspecific mechanism such as the role of free radical scavenger due to its taurine structure. Ca AOTA appears to be a promising drug against alcoholism because of its effects on the multiple targets involved in the mechanism of alcohol dependence. A large multicentric coordinated trial has effectively confirmed the reliability of these pharmacological speculations.
在几种牛磺酸衍生物中，钙N - 乙酰高牛磺酸盐（Ca AOTA）似乎是最有效的抗乙醛和抗酒精剂。对高静脉注射剂量的乙醛或乙醇诱导的小鼠运动减退的拮抗作用以及对大鼠高胃内剂量乙醛致死率的研究表明了它的优越性，在对这些衍生物及其成分进行系统研究后，这种优越性似乎是合乎逻辑的。由于这些磺酸氨基酸的N - 乙酰化导致的神经活动增强作用因靶点而异。由于Ca AOTA对乙醛和乙醇毒性的作用最为显著，这种中枢神经作用首先依赖于其对神经调质、神经介质和阳离子的影响，这些物质主要通过其牛磺酸（TA）结构、γ-氨基丁酸（GABA）激动剂作用、抗阿片受体“纳洛酮样”效应以及作为亚细胞钙载体的可能活性参与酒精依赖机制。Ca AOTA也可能通过其高膜稳定作用发挥作用。与其他化合物相比，它在体外对兔红细胞膜和人羊膜的作用以及在体内对酒精中毒大鼠红细胞膜的作用似乎都是最有效的。在几种对乙醛和乙醇毒性同样有效的牛磺酸衍生物中，Ca AOTA是最好的。它对乙醇最有毒代谢产物的有效性可能特别依赖于乙醛脱氢酶对钙和TA的依赖性，或者依赖于一种非特异性机制，例如由于其牛磺酸结构而具有的自由基清除剂作用。由于Ca AOTA对酒精依赖机制中涉及的多个靶点有作用，它似乎是一种有前景的抗酒精成瘾药物。一项大型多中心协作试验有效地证实了这些药理学推测的可靠性。
