共 103 条
Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5-HT) 2A and DA D2 antagonism and 5-HT1A partial agonism
被引:69
作者:
Huang, Mei
[1
]
Panos, John J.
[1
]
Kwon, Sunoh
[1
]
Oyamada, Yoshihiro
[1
,2
]
Rajagopal, Lakshmi
[1
]
Meltzer, Herbert Y.
[1
]
机构:
[1] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA
[2] Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan
关键词:
acetylcholine;
antipsychotics;
dopamine;
glutamate;
microdialysis;
UPLC-MS;
MS;
MEDIAL PREFRONTAL CORTEX;
RAT FRONTAL-CORTEX;
ATYPICAL ANTIPSYCHOTIC-DRUGS;
REVERSES MK-801-INDUCED IMPAIRMENT;
OBJECT RECOGNITION NOR;
IN-VIVO ACTIONS;
NUCLEUS-ACCUMBENS;
INCREASES DOPAMINE;
RECEPTOR AGONIST;
POTENTIATES HALOPERIDOL;
D O I:
10.1111/jnc.12512
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Atypical antipsychotic drugs (AAPDs) have been suggested to be more effective in improving cognitive impairment in schizophrenia than typical APDs, a conclusion supported by differences in receptor affinities and neurotransmitter efflux in the cortex and the hippocampus. More potent serotonin (5-HT)(2A) than dopamine (DA) D-2 receptors antagonism, and direct or indirect 5-HT1A agonism, characterize almost all AAPDs. Blonanserin, an AAPD, has slightly greater affinity for D-2 than 5-HT2A receptors. Using microdialysis and ultra performance liquid chromatography-mass spectrometry/mass spectrometry, we compared the abilities of the typical APD, haloperidol, three AAPDs, blonanserin, lurasidone, and olanzapine, and a selective 5-HT1A partial agonist, tandospirone, and all, except haloperidol, were found to ameliorate the cognitive deficits produced by the N-methyl-d-aspartate antagonist, phencyclidine, altering the efflux of neurotransmitters and metabolites in the rat cortex and nucleus accumbens. Blonanserin, lurasidone, olanzapine, and tandospirone, but not haloperidol, increased the efflux of cortical DA and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid. Olanzapine and lurasidone increased the efflux of acetylcholine; lurasidone increased glutamate as well. None of the compounds significantly altered the efflux of 5-HT or its metabolite, 5-hydroxyindole acetic acid, or GABA, serine, and glycine. The ability to increase cortical DA efflux was the only shared effect of the compounds which ameliorates the deficit in cognition in rodents following phencyclidine.
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页码:938 / 949
页数:12
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