7-[4-[4-(2,3-Dichlorophenyl)-1-piperazinyl] butyloxy}-3,4-dihydro-2(1H)-quinolinone (OPC-14597): A new antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity.

Kikuchi, Tetsuro; Tottori, Katsura; Uwahodo, Yasufumi; Miwa, Takashi; Hirose, Tetsuro; Fujiwara, Kiyoshi; Oshiro, Yasuo; Morita, Seiji

doi:10.1016/s0021-5198(19)50332-8

Cited by 31 publications

(58 citation statements)

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“…12 This key finding, among others, contributed to the conceptual underpinnings of early psychopharmacological research. Over a decade later, OPC-14597 (aripiprazole), both an agonist at presynaptic dopamine D 2 receptor and an antagonist at postsynaptic dopamine D 2 receptor, 13 which was confirmed to be a dopamine D 2 receptor partial agonist and gained regulatory approval as the world’s first dopamine system stabilizer (DSS) in the USA.…”

Section: Pharmacological Characteristics and Development Of Brexpipramentioning

confidence: 99%

<p>Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist’s Perspective</p>

Watanabe

Yamada²,

Otsubo³

et al. 2020

DDDT

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While the prognosis of patients with schizophrenia has dramatically improved after the advent of chlorpromazine, the antipsychotics currently available are so numerous that it has become a challenge for psychiatrists to choose from among these drugs for each patient presenting for care. In addition, while numerous studies show that an effective antipsychotic should be continued indefinitely to prevent relapses or worsening, many patients appear to have difficulty remaining on any drug thus initiated. Brexpiprazole, a dopamine D 2 receptor partial agonist, appears to provide a unique profile that has much to offer in this light. Specifically, this novel drug is potentially better suited for long-term use, with decreased risk of extrapyramidal side effects, hyperprolactinemia, weight gain, psychosis, insomnia, akathisia, nausea/vomiting or restlessness, thus potentially facilitating patients’ reintegration into society. Indeed, brexpiprazole has been shown in randomized, double-blind, placebo-controlled trials to have proven efficacy not only in improving the symptoms of schizophrenia but in preventing relapses. It is also suggested in both short- and long-term studies that brexpiprazole offers a favorable safety and tolerability profile. This review also includes a proposed treatment algorithm incorporating brexpiprazole, based on the clinical trial results available, as well as on the authors’ clinical experience, where brexpiprazole may be best used as a drug of first choice for the treatment of schizophrenia. Thus, overall, brexpiprazole appears to play a more significant role in the treatment of schizophrenia than other antipsychotics.

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Section: Pharmacological Characteristics and Development Of Brexpipramentioning

confidence: 99%

<p>Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist’s Perspective</p>

Watanabe

Yamada²,

Otsubo³

et al. 2020

DDDT

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“…The effects in the cognitive tests are superior to those of aripiprazole [Maeda et al 2014b]. The potency of brexpiprazole to induce antipsychotic-like activity is in the same range as that predicting in vivo D 2 receptor occupancy [Maeda et al 2014b]; cataleptogenic activity is only induced at high dosages likely due to D 2 partial agonism and its 5-HTergic activities [Kikuchi et al 1995; Meltzer 1999]. Similar to aripiprazole, brexpiprazole has low potential to induce EPS at relevant clinical exposures, leading to 60–90% D 2 receptor occupancy [Yokoi et al 2002].…”

Section: Preclinical Insightsmentioning

confidence: 99%

Brexpiprazole: so far so good

Das

Barnwal

et al. 2015

Therapeutic Advances in Psychopharmacology

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This article describes the role of a newly approved antipsychotic agent brexpiprazole in the treatment of schizophrenia and major depressive disorder. This drug has high affinity for 5-HT 1A , 5-HT 2A , D 2 and α 1B,2C receptors. It displays partial agonism at 5-HT 1A and D 2 receptors and potent antagonism at 5-HT 2A and α 1B,2C adrenergic receptors. It also has some affinity (antagonism) for D 3 , 5-HT 2B , 5-HT 7 and α 1A,1D receptors, and moderate affinity for H 1 and low affinity for M 1 receptors. These all lead to a favorable antipsychotic profile in terms of improvement of cognitive performance and sleep patterns, as well as effects on affective states and potential to treat core symptoms in schizophrenia and major depressive disorder, including cognitive deficits with a low risk of adverse effects (extrapyramidal symptoms, metabolic complications, weight gain, akathisia potential) that are commonly encountered with other typical and second-generation antipsychotic drugs. In our review, we have made an attempt to decipher the pharmacological profile of brexpiprazole from two major trials (VECTOR and BEACON). We have also tried to give a concise but detailed overview of brexpiprazole by head to head comparison of the pharmacological profile of brexpiprazole and its earlier congeners aripiprazole and prototype antipsychotic drug chlorpromazine by accessing individual summaries of product characteristics from the US Food and Drug Administration database, 2015. Relevant preclinical and clinical studies associated with this drug have been discussed with emphasis on efficacy and safety concerns. From the studies done so far, it can be concluded that brexpiprazole can be an effective monotherapy for schizophrenia and as an adjunct to other antidepressant medications in major depressive disorder.

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“…Preclinical studies classified aripiprazole as a potent D2 receptor partial agonist (Burris et al , 2002). Additional evidence of aripiprazole's partial agonist properties was gained from animal models of dopamine hyperactivity and hypoactivity: aripiprazole demonstrated antagonism of D2 receptors by suppressing apomorphine-induced stereotypy (dopamine hyperactivity model), and D2 agonist properties by blocking enhanced dopamine synthesis in rats treated with reserpine (dopamine hypoactivity model) (Kikuchi et al , 1995). The stabilising effect of aripiprazole on the dopamine system was attributed to its targeting of presynaptic (autoreceptors) and post-synaptic D2 receptors.…”

Section: Partial Agonists: Old and Newmentioning

confidence: 99%

Partial agonism and schizophrenia

Bolonna

Kerwin

2005

Br J Psychiatry

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Recent literature on partial agonists has Recent literature on partial agonists has generated interest in their therapeutic generated interest in their therapeutic potential in schizophrenia. This has been potential in schizophrenia. This has been driven, in part, by the recent approval of driven, in part, by the recent approval of the dopamine (D2) receptor partial agonist the dopamine (D2) receptor partial agonist aripiprazole in the USA and Europe. In aripiprazole in the USA and Europe. In comparison with conventional and atypical comparison with conventional and atypical antipsychotics that mediate their therapeuantipsychotics that mediate their therapeutic effects by D2 receptor blockade, aripitic effects by D2 receptor blockade, aripiprazole has a unique mechanism of action. prazole has a unique mechanism of action. However, the concept of partial agonists However, the concept of partial agonists for the treatment of schizophrenia is not for the treatment of schizophrenia is not entirely novel, since aripiprazole is one of entirely novel, since aripiprazole is one of several members of this class of drug. This several members of this class of drug. This editorial reviews the neurochemistry of editorial reviews the neurochemistry of dopamine in schizophrenia and discusses dopamine in schizophrenia and discusses the theoretical importance of partial agonthe theoretical importance of partial agonism as a mechanism for the treatment of ism as a mechanism for the treatment of this illness. We also summarise the historithis illness. We also summarise the historical information on previous trials of partial cal information on previous trials of partial agonists in schizophrenia and evaluate agonists in schizophrenia and evaluate other dopamine receptor partial agonists other dopamine receptor partial agonists that are currently under development. that are currently under development.

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7-[4-[4-(2,3-Dichlorophenyl)-1-piperazinyl] butyloxy}-3,4-dihydro-2(1H)-quinolinone (OPC-14597): A new antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity.

Cited by 31 publications

References 0 publications

<p>Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist’s Perspective</p>

<p>Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist’s Perspective</p>

Brexpiprazole: so far so good

Partial agonism and schizophrenia

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