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.
Ohno
Y
Y
Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Ishida
K
K
Ikeda
K
K
Ishibashi
T
T
Okada
K
K
Nakamura
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology* / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011597:Psychomotor Performance / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D054833:Isoindoles; D012702:Serotonin Antagonists; D013844:Thiazoles; C065533:perospirone