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.