Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents

@article{Gyertyn2011CariprazineA,
  title={Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents},
  author={Istv{\'a}n Gyerty{\'a}n and B{\'e}la Kiss and Katalin Sághy and Judit Laszy and Gy{\"o}rgy Szab{\'o} and Tam{\'a}s Szabados and Larisza I. Gémesi and Gabriella P{\'a}sztor and M{\'a}ria Z{\'a}jer-Bal{\'a}zs and Margit Kapás and {\'E}va {\'A}gai Csongor and György Domány and Károly Tihanyi and Zsolt Szombathelyi},
  journal={Neurochemistry International},
  year={2011},
  volume={59},
  pages={925-935}
}
The Role of Dopamine D3 Receptor Partial Agonism in Cariprazine-Induced Neurotransmitter Efflux in Rat Hippocampus and Nucleus Accumbens
TLDR
The results suggested D3 receptor partial agonist activity of cariprazine, producing functional antagonism, may contribute to its efficacy in schizophrenia and bipolar disorder.
Cariprazine (RGH-188), a D3-preferring dopamine D3/D2 receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats
TLDR
Results in rats with a history of cocaine self-administration after a period of complete abstinence in a relapse to cocaine-seeking paradigm may predict a relapse-preventing action for cariprazine in humans in addition to its existing antipsychotic and antimanic efficacy.
Clinical potential of cariprazine in the treatment of acute mania.
TLDR
The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date.
Brain uptake and distribution of the dopamine D3/D2 receptor partial agonist [11C]cariprazine: An in vivo positron emission tomography study in nonhuman primates
TLDR
The data confirm that cariprazine, a novel antipsychotic drug candidate, enters the nonhuman primate brain readily and binds to dopamine D3/D2 receptors.
Cariprazine for the Treatment of Schizophrenia: A Review of this Dopamine D3-Preferring D3/D2 Receptor Partial Agonist.
  • L. Citrome
  • Psychology, Medicine
    Clinical schizophrenia & related psychoses
  • 2016
TLDR
Cariprazine is an antipsychotic medication and received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in September 2015; the starting dose of 1.5 mg/d is potentially therapeutic.
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
TLDR
This PET imaging study in patients with schizophrenia demonstrated that cariprazine is a D3-preferring dual D3/D2 receptor partial agonist.
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 pharmacodynamic and pharmacokinetic characterization of the major metabolites of cariprazine
TLDR
Overall, in vitro and in vivo pharmacological profiles of DCAR and DDCAR demonstrated high similarity with cariprazine, suggesting that the major metabolites of carIPrazine contribute significantly to its clinical efficacy.
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Cariprazine (RGH-188), a Dopamine D3 Receptor-Preferring, D3/D2 Dopamine Receptor Antagonist–Partial Agonist Antipsychotic Candidate: In Vitro and Neurochemical Profile
TLDR
The antagonist–partial agonist properties of cariprazine at D3 and D2 receptors, with very high and preferential affinity to D3 receptors, make it a candidate antipsychotic with a unique pharmacological profile among known antipsychotics.
Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: II. behavioural characterisation of RG-15
TLDR
The results suggest that subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity may result in an antipsychotic profile characterised by a lack of extrapyramidal side effects and secondary negative symptoms with simultaneous efficacy on positive and cognitive symptoms of schizophrenia.
Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15
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Neurochemical comparison of RG-15 with antagonists having a different affinity and selectivity toward D3 and D2 receptors indicate that D3 receptors have little, if any, role in the control of presynaptic dopamine biosynthesis/release in dopaminergic terminal regions.
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TLDR
The effect of SB-277011-A on isolation-induced prepulse inhibition deficit suggests that blockade of dopamine D(3) receptors may benefit the treatment of schizophrenia.
Cariprazine (RGH-188), a D3-preferring dopamine D3/D2 receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats
TLDR
Results in rats with a history of cocaine self-administration after a period of complete abstinence in a relapse to cocaine-seeking paradigm may predict a relapse-preventing action for cariprazine in humans in addition to its existing antipsychotic and antimanic efficacy.
The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent.
TLDR
It is predicted that olanzapine will have an atypical profile and will be less likely to induce undesirable extrapyramidal symptoms than currently available drugs.
Effects of a novel, selective, σ1-ligand, MS-377, on phencyclidine-induced behaviour
TLDR
The results suggest that there are at least two types of ligands for σ1-receptors and that some ρ1-ligands, including MS-377, have more comprehensive effects against PCP-induced abnormal behaviour than other σ 1-ligand or D2 antagonists.
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