Alteration of the brain morphology and the response to the acute stress in the recombinant mouse lines with different predisposition to catalepsy

PCC0104005 is a novel drug candidate for treating schizophrenia that displays high affinity for serotonin, dopamine, and noradrenaline receptors, including partial agonism at dopamine D2, D3, D4, serotonin 5-HT1A, and 5-HT2A receptors and antagonism at 5-HT2B, 5-HT6, and 5-HT7 receptors. PCC0104005 blocks MK-801-induced hyperactivity in rats, consistent with the reduction in dopamine D2 receptor stimulation and increased dopamine release in the medial prefrontal cortex. PCC0104005 inhibits 5-HTP-induced head twitches in rats, due to its moderate affinity for human 5-HT2A receptors (Ki = 5.1 nM). PCC0104005 significantly reduced the escape latency of rats and improved the MK-801-induced memory impairment. In the object recognition experiment, PCC0104005 significantly improved the recognition disorder induced by MK-801. PCC0104005 did not significantly increase the plasma prolactin level, which is thought to be related to the preferential affinity of PCC0104005 for dopamine D2 receptors compared with 5-HT1A receptors, as well as the relative antagonistic activity toward the D2 receptor. Due to its 5-HT1A agonism, PCC0104005 does not produce catalepsy in mice, a behaviour predictive of the occurrence of extra-pyramidal syndrome (EPS) in humans. PCC0104005 has unique affinities for dopamine receptors and serotonin receptors, which may lead to clinical advantages, as well as fewer adverse reactions.

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“…The experiment was repeated at least 10 times. Finally, the longest period of catalepsy for each mouse was recorded 40 .…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Characterization of PCC0104005, a Novel Modulator of Serotonin-Dopamine Activity, as an Atypical Antipsychotic Drug

Zhu

Wang

et al. 2018

Sci Rep

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Effects of Acute Stress in Mice with 5-HT1A Receptors with Different Sensitivities to Chronic Activation by 8-OH-DPAT

Кондаурова

Antonov

Bazhenova

et al. 2021

Neurosci Behav Physi

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Acute stress effect on hypothalamus BDNF expression, monoamines levels and adrenal catecholamines in mouse lines differed by 5-HT1A receptor function

Кондаурова

Antonov

Pershina

et al. 2019

European Neuropsychopharmacology

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Alteration of the brain morphology and the response to the acute stress in the recombinant mouse lines with different predisposition to catalepsy

Cited by 10 publications

References 28 publications

In Vitro and In Vivo Characterization of PCC0104005, a Novel Modulator of Serotonin-Dopamine Activity, as an Atypical Antipsychotic Drug

In Vitro and In Vivo Characterization of PCC0104005, a Novel Modulator of Serotonin-Dopamine Activity, as an Atypical Antipsychotic Drug

Effects of Acute Stress in Mice with 5-HT1A Receptors with Different Sensitivities to Chronic Activation by 8-OH-DPAT

Acute stress effect on hypothalamus BDNF expression, monoamines levels and adrenal catecholamines in mouse lines differed by 5-HT1A receptor function

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