Abstract |
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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Authors | Yanan Xu, Xiaoyin Zhu, Hongbo Wang, Shanyue Sun, Xin Yue, Jingwei Tian |
Journal | Scientific reports
(Sci Rep)
Vol. 8
Issue 1
Pg. 6892
(05 02 2018)
ISSN: 2045-2322 [Electronic] England |
PMID | 29720711
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Biomarkers
- Dopamine Agents
- Receptors, Dopamine
- Receptors, Serotonin
- Serotonin Agents
- Dizocilpine Maleate
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Topics |
- Animals
- Antipsychotic Agents
(chemistry, pharmacology)
- Behavior, Animal
(drug effects)
- Biomarkers
- Dizocilpine Maleate
(pharmacology)
- Dopamine Agents
(chemistry, pharmacology)
- Hyperkinesis
(drug therapy, metabolism)
- Male
- Maze Learning
(drug effects)
- Memory
(drug effects)
- Mice
- Rats
- Receptors, Dopamine
(metabolism)
- Receptors, Serotonin
(metabolism)
- Recognition, Psychology
(drug effects)
- Serotonin Agents
(chemistry, pharmacology)
- Temperature
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