Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties

@article{NewmanTancredi2011ComparativePO,
  title={Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties},
  author={Adrian Newman-Tancredi and Mark S. Kleven},
  journal={Psychopharmacology},
  year={2011},
  volume={216},
  pages={451-473}
}
RationaleThere is increasing interest in antipsychotics intended to manage positive symptoms via D2 receptor blockade and improve negative symptoms and cognitive deficits via 5-HT1A activation. Such a strategy reduces side-effects such as the extrapyramidal syndrome (EPS), weight gain, and autonomic disturbance liability.ObjectiveThis study aims to review pharmacological literature on compounds interacting at both 5-HT1A and D2 receptors (as well as at other receptors), including aripiprazole… 
Improving the treatment of schizophrenia: role of 5-HT receptors in modulating cognitive and extrapyramidal motor functions.
TLDR
The functional roles and mechanisms of 5-HT receptors in the treatment of schizophrenia are reviewed, focusing on the serotonergic modulation of cognitive and extrapyramidal motor functions, and illustrates future therapeutic strategies.
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Selectivity
TLDR
A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms.
Classics in Chemical Neuroscience: Aripiprazole.
TLDR
Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D2 and D3 and serotonin 5-HT1A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects.
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TLDR
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TLDR
Compared with olanzapine, lurasidone preferentially binds to D2/D3 receptors rather than 5-HT2A receptors in common marmosets, suggesting that the contribution of in vivo 5- HT2A receptor blocking activity to the pharmacological profile of lurasIDone might differ from olanZapine in terms of the low risk of extrapyramidal syndrome and efficacy against negative symptoms.
Serotonin 5-HT1A Receptors as Targets for Agents to Treat Psychiatric Disorders: Rationale and Current Status of Research
TLDR
In agreement with pharmacological studies, presynaptic and postsynaptic 5- HT1A-R activation appears necessary for anxiolytic and antidepressant effects, respectively, yet, neurodevelopmental roles for 5-HT 1A-Rs are also involved.
Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator
TLDR
The results indicate that brexpiprazole has antipsychotic-like activity and robust efficacy in relevant models of cognitive impairment associated with schizophrenia, and the pharmacologic profile of brexpIPrazole is proposed to be based on its balanced effects on 5-HT1A, D2, and 5- HT2A receptors, with possible modulating activity through additional monoamine receptors.
Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex
TLDR
Ketamine was used to induce cognitive deficits in mice and confirmed the co-localization of D2/5- HT1A and 5-HT1A/5 -HT2A receptors in the mouse cortex, and affected the formation of GPCR heterodimers, which are new targets for the treatment of schizophrenia.
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