PHARMACOTOXICOLOGICAL ASPECTS OF LEVOSULPIRIDE

Levosulpiride is the levorotatory enantiomer of sulpiride, a substitut ed benzamide indicated as an antipsychotic, antidepressant, antiemetic and antidyspeptic drug, as well as for the treatment of somatoform di sorders. In vivo sulpiride displays a number of neuroleptic properties which it shares with all typical neuroleptic drugs; however, it has a lso a number of divergent characteristics that set it apart as the pri ncipal compound of the so-called 'atypical neuroleptic agents'. The ma in mechanism of action of levosulpiride consists of blocking the D-2 d opaminergic receptors, preferentially located on the presynaptic membr anes in the dopaminergic pathways of the brain; this means that sulpir ide is a selective autoreceptor blocker. The results of series of expe rimental 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, mutag enic potential and oncogenic/carcinogenic potential, demonstrate that levosulpiride is well tolerated by the animals tested (rats, mice, rab bits 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 prec linical studies, levosulpiride shows pharmacotoxicologic properties wh ich make it suitable for the management of diseases for which the drug is indicated.