Effects of SM-9018, a novel 5-HT2 and D2 receptor antagonist, on electrically-evoked [3H]acetylcholine release from rat striatal slices.
1. Electrical stimulation (1 Hz) of striatal slices evoked Ca(+2)-dependent [3H]ACh release, which was inhibited by the D2 agonist quinpirole (QPL). 2. SM-9018 and other neuroleptics antagonized the QPL-induced inhibition of the evoked [3H]ACh release. The relative potencies of the neuroleptics in antagonizing the QPL action were nemonapride > haloperidol approximately equal to SM-9018 > > chlorpromazine > > SCH 23390, and the rank order, except for nemonapride, was consistent with their binding affinities to striatal D2 receptors. 3. SM-9018 was weaker than haloperidol in enhancing the [3H]ACh release evoked by higher frequency (3 Hz) stimulation, the enhancement being abolished by the depletion of endogenous dopamine with reserpine pretreatment. 4. The selective 5-HT2 antagonist LY 53857 significantly attenuated the stimulatory effects of haloperidol on the 3 Hz-evoked [3H]ACh release. 5. These findings suggest that SM-9018 is as potent as haloperidol in antagonizing the QPL action on [3H]ACh release at striatal D2 receptors, but is weaker than haloperidol in enhancing the [3H]ACh release under high-frequency stimulation. The 5-HT2 blocking activity of SM-9018 seems to be involved in the latter effects.
Ishida
K
K
Discovery Research Laboratories II, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Ohno
Y
Y
Ishibashi
T
T
Nakamura
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019257:Quinpirole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D054833:Isoindoles; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D013844:Thiazoles; D019257:Quinpirole; D006220:Haloperidol; C065533:perospirone; D000109:Acetylcholine