@article{APS9440,
author = {Xue SUN and Hong-yan GOU and Fei LI and Guan-yi LU and Rui SONG and Ri-fang YANG and Ning WU and Rui-bin SU and Bin CONG and Jin LI},
title = {Y-QA31, a novel dopamine D3 receptor antagonist, exhibits antipsychotic-like properties in preclinical animal models of schizophrenia},
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {3},
year = {2017},
keywords = {},
abstract = {Aim: To investigate the potential effects of Y-QA31, a novel dopamine D3 receptor antagonist, as an antipsychotic drug.
Methods: A panel of radioligand-receptor binding assays was performed to identify the affinities of Y-QA31 for different G proteincoupled receptors. [35S]GTPγS-binding assays and Ca2+ imaging were used to assess its intrinsic activities. The antipsychotic profile of Y-QA31 was characterized in mouse models for the positive symptoms and cognitive deficits of schizophrenia and extrapyramidal side effects with haloperidol and clozapine as positive controls.
Results: In vitro, Y-QA31 is a dopamine D3 receptor antagonist that is 186-fold more potent at the D3 receptor than at the D2 receptor. Y-QA31 also exhibits 5-HT1A receptor partial agonist and α1A adrenoceptor antagonist activities with medium affinity, whereas it exhibits very little affinity for other receptors (100-fold lower than for the D3 receptor). In vivo, Y-QA31 (10–40 mg/kg, po) significantly inhibited MK-801-induced hyperlocomotion and methamphetamine-induced prepulse inhibition disruption in a dose-dependent manner. Y-QA31 also inhibited the avoidance response and methamphetamine-induced hyperlocomotion with potency lower than haloperidol. Y-QA31 was effective in alleviating the MK-801-induced disruption of novel object recognition at a low dose (1 mg/kg, po). Moreover, Y-QA31 itself did not affect spontaneous locomotion or induce cataleptic response until its dose reached 120 mg/kg.
Conclusion: Y-QA31 is a selective D3R antagonist that exhibits antipsychotic effects in some animal models with positive symptoms and cognitive disorder and less extrapyramidal side effects.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9440}
}