Evaluation of bradykinesia induction by SM-9018, a novel 5-HT2 and D2 receptor antagonist, using the mouse pole test.

Induction of bradykinesia by SM-9018, a novel 5-HT2 and D2 antagonist, was compared with that of other neuroleptics using the pole test in mice. Neuroleptics including SM-9018, haloperidol, chlorpromazine, and thioridazine dose dependently induced bradykinesia in the pole-descending behavior of mice with relative potencies consistent with those for catalepsy induction. SM-9018 was about 70 times weaker than haloperidol and twice as weak as thioridazine in inducing bradykinesia. Other CNS drugs such as barbiturates and antidepressants had no effects. Haloperidol-induced bradykinesia was significantly attenuated by a cholinergic muscarinic antagonist (i.e., trihexyphenidyl) and 5-HT2 antagonists (i.e., ritanserin and cyproheptadine) whereas that caused by SM-9018 was relatively resistant to the 5-HT2 antagonists. These findings suggest that SM-9018 is weaker than other neuroleptics in inducing extrapyramidal side effects and that the 5-HT2 blocking activity of SM-9018 may contribute to its atypical neuroleptic property.