Objective: Several classes of prescription drugs contribute to the sexual dysfunction in men that have been found especially in the antipsychotic drugs. Varieties of mechanisms are likely to contribute to the antipsychotic-related sexual dysfunction including hyperprolactinemia and antagonism of some neurotransmitter receptors. Implications for future research, atypical antipsychotics should be strongly taken into account. Material and Method: Male mice were treated by intraperitoneal injection (IP injection) of drugs for 21 days. The effects of saline, quetiapine, olanzapine, and risperidone were investigated on serotonin, noradrenaline (NA), adenosine triphosphate (ATP) and potassium chloride (KCl) which induced contractions of the vas deferens. Results: Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portion of the vas deferens obtained from the risperidone-treated group. The Emax value for serotonin was significantly higher in prostatic and epididymal portions of the mice vas deferens obtained from the risperidone-treated group than the control group. However, olanzapine and quetiapine treatment had no effect on serotonin responses in both epididymal and prostatic portions of the mice vas deferens. The risperidone treatment significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens. There were no significant differences in KCl-induced contractile responses among the groups. Conclusion: It can be concluded that only risperidone could impair sexual competence in the male mice. Serotonergic, noradrenergic and purinergic receptors may contribute to the changes in vas deferens contractions in mice with chronic treatment of risperidone but not olanzapine and quetiapine. This study will help clinicians make a purpose-oriented choice of which antipsychotic drug to use.