Rossi F, Forgione A
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, Second University of Naples, Italy.
Pharmacol Res. 1995 Feb;31(2):81-94. doi: 10.1016/1043-6618(95)80052-2.
Levosulpiride is the levorotatory enantiomer of sulpiride, a substituted benzamide indicated as an antipsychotic, antidepressant, antiemetic and antidyspeptic drug, as well as for the treatment of somatoform disorders. In vivo sulpiride displays a number of neuroleptic properties which it shares with all typical neuroleptic drugs; however, it has also a number of divergent characteristics that set it apart as the principal compound of the so-called 'atypical neuroleptic agents'. The main mechanism of action of levosulpiride consists of blocking the D2 dopaminergic receptors, preferentially located on the presynaptic membranes in the dopaminergic pathways of the brain; this means that sulpiride is a selective autoreceptor blocker. The results of series of experimental trials conducted to evaluate the toxicologic characteristics of levosulpiride are presented. Both the acute, subacute, chronic and local toxicity trials, and the studies on reproduction toxicity, mutagenic potential and oncogenic/carcinogenic potential, demonstrate that levosulpiride is well tolerated by the animals tested (rats, mice, rabbits and dogs) at doses higher than those effective in human therapy. Moreover, the findings from the experimental studies on levosulpiride lead to exclude the toxicity from accumulation, tolerance, dependence or withdrawal syndrome. In conclusion, according to the evaluated preclinical studies, levosulpiride shows pharmacotoxicologic properties which make it suitable for the management of diseases for which the drug is indicated.
左舒必利是舒必利的左旋对映体，舒必利是一种取代苯甲酰胺，用作抗精神病药、抗抑郁药、止吐药和抗消化不良药，也用于治疗躯体形式障碍。在体内，舒必利表现出许多与所有典型抗精神病药物共有的抗精神病特性；然而，它也有一些不同的特征，使其成为所谓“非典型抗精神病药物”的主要化合物。左舒必利的主要作用机制包括阻断D2多巴胺能受体，这些受体优先位于大脑多巴胺能通路的突触前膜上；这意味着舒必利是一种选择性自身受体阻滞剂。本文介绍了一系列评估左舒必利毒理学特性的实验试验结果。急性、亚急性、慢性和局部毒性试验，以及生殖毒性、致突变潜力和致癌/致瘤潜力研究均表明，在高于人类治疗有效剂量的情况下，受试动物（大鼠、小鼠、兔子和狗）对左舒必利耐受性良好。此外，关于左舒必利的实验研究结果排除了其具有蓄积毒性、耐受性、依赖性或戒断综合征的可能性。总之，根据评估的临床前研究，左舒必利显示出的药物毒理学特性使其适用于治疗该药物所适用的疾病。
