Pharmacotoxicological aspects of levosulpiride.
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.
Rossi
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Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, Second University of Naples, Italy.
Forgione
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012098:Reproduction / Q000187:drug effects; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D018675:Toxicity Tests; D014554:Urination / Q000187:drug effects
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013469:Sulpiride; C078143:levosulpiride