Brexpiprazole I: In Vitro and In Vivo Characterization of a Novel Serotonin-Dopamine Activity Modulator

@article{Maeda2014BrexpiprazoleII,
  title={Brexpiprazole I: In Vitro and In Vivo Characterization of a Novel Serotonin-Dopamine Activity Modulator},
  author={Kenji Maeda and Haruhiko Sugino and Hitomi Akazawa and Naoki Amada and Jun Shimada and Takashi Futamura and Hiroshi Yamashita and Nobuaki Ito and Robert Mcquade and Arne M{\o}rk and Alan L Pehrson and Morten Hentzer and Vibeke Nielsen and Christoffer Bundgaard and J{\o}rn Arnt and Tine Bryan Stensb{\o}l and Tetsuro Kikuchi},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2014},
  volume={350},
  pages={589 - 604}
}
Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel drug candidate in clinical development for psychiatric disorders with high affinity for serotonin, dopamine, and noradrenaline receptors. In particular, it bound with high affinity (Ki < 1 nM) to human serotonin 1A (h5-HT1A)-, h5-HT2A-, long form of human D2 (hD2L)-, hα1B-, and hα2C-adrenergic receptors. It displayed partial agonism at h5-HT1A and hD2 receptors in cloned receptor systems… 
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221 Citations
Highly Influential Citations
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Methods Citations
8
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221 Citations

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.
Acute Effects of Brexpiprazole on Serotonin, Dopamine, and Norepinephrine Systems: An In Vivo Electrophysiologic Characterization
TLDR
In conclusion, the in vivo action of brexpiprazole on monoamine targets relevant in the treatment of depression and schizophrenia is assessed and α1- and α2-adrenergic receptors are evaluated.
Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: A role for serotonin 5-HT1A receptors
Involvement of 5-HT1A and 5-HT2A Receptors but Not α2-Adrenoceptors in the Acute Electrophysiological Effects of Cariprazine in the Rat Brain In Vivo
TLDR
Results indicate that, in vivo, cariprazine acted as a 5-HT1A autoreceptor agonist in the DRN, a5-HT2A receptor antagonist in modulating the firing activity of LC NE neurons, and a full agonist at 5- HT1A receptors mediating the electrophysiological effect of 5-hydroxytryptamine on pyramidal neurons.
Preclinical characterization of ACH-000029, a novel anxiolytic compound acting on serotonergic and alpha-adrenergic receptors
Investigating the Potential Role of Serotonin-2B Receptor Antagonism in the Neuronal Actions of Adjunctive Aripiprazole
TLDR
5-HT2B receptor blockade rescues an SSRI-mediated decrease in DA firing activity and increases mPFC pyramidal neuron firing and bursting activity mediated by aripiprazole and in combination with escitalopram may be, at least partly, moderated by 5- HT2B receptors expressed in this brain area.
In Vitro and In Vivo Characterization of PCC0104005, a Novel Modulator of Serotonin-Dopamine Activity, as an Atypical Antipsychotic Drug
TLDR
PCC0104005 has unique affinities for dopamine receptors and serotonin receptors, which may lead to clinical advantages, as well as fewer adverse reactions.
Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin–dopamine activity modulator: A role for serotonin 5-HT1A and 5-HT2A receptors
In vitro evaluations for pharmacokinetic drug-drug interactions of a novel serotonin-dopamine activity modulator, brexpiprazole
TLDR
In vitro data suggest that brexpiprazole is unlikely to cause clinically relevant drug interactions resulting from the effects on CYPs or transporters mediating the absorption, metabolism, and/or disposition of co-administered drugs.
Involvement of presynaptic 5-HT1A receptors in the low propensity of brexpiprazole to induce extrapyramidal side effects in rats
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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.
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