Quetiapine, iloperidone, melperone selectively increase dopamine/acetylcholine - Antipsychotic Drugs

15 февраля, 2003
According to recent research from the United States, "preferential increases in both cortical dopamine and acetylcholine release have been proposed to distinguish the atypical antipsychotic drugs clozapine, olanzapine, risperidone, and ziprasidone from typical APDs such as haloperidol. Drug Week via NewsEdge Corporation : According to recent research from the United States, "preferential increases in both cortical dopamine (DA) and acetylcholine (ACh) release have been proposed to distinguish the atypical antipsychotic drugs (APDs) clozapine, olanzapine, risperidone, and ziprasidone from typical APDs such as haloperidol. Although only clozapine and ziprasidone are directly acting 5-HT1A agonists; WAY100635, a selective 5-HT1A antagonist, partially attenuates these atypical APD induced increases in cortical DA release that may be due to combined blockade. However, WAY100635 does not attenuate clozapine induced cortical ACh release. "The present study determined whether quetiapine, iloperidone, and melperone; 5-HT2A/D-2 antagonist atypical APDs, also increase cortical DA and ACh release, and whether these effects are related to 5-HT1A agonism. Quetiapine (30 mg/kg), iloperidone (1-10 mg/kg), and melperone (3-10 mg/kg) increased DA and ACh release in the medial prefrontal cortex (mPFC). Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine (30 mg/kg), produced an equivalent or a smaller increase in DA release in the nucleus accumbens (NAC), respectively, compared to the mPFC; whereas none of them increased ACh release in the NAC. WAY100635 (0.2 mg/kg), which alone did not affect DA or ACh release, partially attenuated quetiapine (30 mg/kg), iloperidone (10 mg/kg), and melperone (10 mg/kg) induced DA release in the mPFC. WAY100635 also partially attenuated quetiapine (30 mg/kg) induced ACh release in the mPFC, but not that induced by iloperidone (10 mg/kg) or melperone (10 mg/kg)," wrote J. Ichikawa. The researchers concluded: "These results indicate that quetiapine, iloperidone and melperone preferentially increase DA release in the mPFC, compared to the NAC via a 5-HT1A-related mechanism. However, 5-HT1A agonism may be important only for quetiapine-induced ACh release." Ichikawa and colleagues published their study in Brain Research (Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: Role of 5-HT1A receptor agonism. Brain Res, 2002;956(2):349-357). For additional information, contact J. Ichikawa, Hospital of Psychiatry, 1601 23rd Avenue S, 1st Floor Laboratory, Room 1117, Nashville, TN 37212, USA. To subscribe to the journal Brain Research, contact the publisher: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands. The information in this article comes under the major subject areas of Dopamine, Acetylcholine, Drugs and Antipsychotic Therapy. This article was prepared by Drug Week editors from staff and other reports. <> << Copyright ©2003 NewsRx.com >>