Aripiprazole: from pharmacological profile to clinical use

Sciascio, Guido Di; Riva, Marco A.

doi:10.2147/ndt.s88117

Cited by 37 publications

(31 citation statements)

References 84 publications

(107 reference statements)

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“…Interestingly, PAC1-overexpression mice have been reported to display strikingly similar phenotypes to PAC1 knockout mice [42], suggesting that the changes in the expression of PACAPergic signaling observed in schizophrenic patients seem to be very complex, and associated with defects or overexpression of PAC1. The conventional drugs which are used to treat schizophrenia or potential candidates may restore the normal conditions for PACAP-PAC1 signaling in the brain, perhaps by acting like partial agonists [43]. …”

Section: Discussionmentioning

confidence: 99%

Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors

Jóźwiak-Bębenista

Kowalczyk

2016

Neurochem Res

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Several lines of evidence suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide playing an important role as a neuromodulator. It has been indicated that PACAP is associated with mental diseases, and that regulation of the PACAPergic signals could be a potential target for the treatment of such psychiatric states as schizophrenia. Recent studies have suggested that action of neuroleptic drugs is mediated not only by dopaminergic and serotonergic neurotransmission, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators. The present study examines whether currently-used neuroleptics influence the action of PACAP receptors, whose expression is altered in a schizophrenic patient. Real-time polymerase chain reaction (PCR) was used to examine the effects of haloperidol, olanzapine and amisulpride on the expression of genes coding PAC1/VPAC type receptors in the T98G glioblastoma cell line, as an example of an in vitro model of glial cells. PAC1 mRNA expression fell after 24-h incubation with haloperidol or olanzapine; however the effect was not maintained after 72 h, and haloperidol even up-regulated PAC1 mRNA expression in a dose-dependent manner. All the examined drugs decreased VPAC2 mRNA expression, especially after 72-h incubation. Haloperidol (typical neuroleptic) was distinctly more potent than atypical neuroleptic drugs (olanzapine and amisulpride). In addition, PACAP increased PAC1 and VPAC2 mRNA expression. In conclusion, our findings suggest PACAP receptors may be involved in the mechanism of typical and atypical neuroleptic drugs.

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Section: Discussionmentioning

confidence: 99%

Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors

Jóźwiak-Bębenista

Kowalczyk

2016

Neurochem Res

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“…50 Besides partial agonist activity at D 2 receptors, aripiprazole’s agonist activity at 5-HT 1A receptors, from partial to full agonist depending on cellular system, may also contribute to its efficacy and reduced side effects, relative to FGAs. 46–47, 62, 101, 116–118 Aripiprazole activates somatodendritic 5-HT 1A receptors, reducing serotonin release and subsequently increasing dopamine release in the cortex, which may translate to treat negative and cognitive symptoms of schizophrenia. 119–120 Similarly, SGAs, such as clozapine and ziprasidone, that can attenuate negative and cognitive symptoms are also 5-HT 1A partial agonists 121–123 and enhance central dopamine release via activation of 5-HT 1A receptors.…”

Section: Pharmacology and Adverse Eventsmentioning

confidence: 99%

Classics in Chemical Neuroscience: Aripiprazole

Casey

Canal

2017

ACS Chem. Neurosci.

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Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D2 receptor binding kinetics, have significantly lower risk of movement side effects, but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole’s polypharmacology—characterized by its unique agonist activity at dopamine D2, D3 and serotonin 5-HT1A receptors as well as antagonist activity at serotonin 5-HT2A receptors—translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole’s neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.

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“…These receptors, in particular, strongly present at mesolimbic level, could explain the problems of impulse dysregulation related to treatment with ARI or dopamine agonists (pramipexole and ropinirole) (4). Its widespread use is given not only by a large number of existing formulations (capsules with various dosages, solution, vials, depot) but also because of its good safety profile (especially in terms of cardiac safety) (5).…”

Section: Introductionmentioning

confidence: 99%

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis

et al. 2020

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Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARIinduced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of both GD and ARI's clinical response to a genetic polymorphism on the D2 receptor (DRD2/ANKK1 Taq1A; rs1800497), the hypothesis regarding the origin of this phenomenon could be found in the altered sensitization of dopamine's receptors that certain individuals carry genetically. The identification of a possible genetic susceptibility (detectable by genetic tests) could provide clinicians with an explanation for the ARI-induced GD and the possibility of using genetic screening tools for those cases of suspected predisposition; this would allow the clinician to prescribe ARI with less apprehension. The confirmation of this hypothesis through future pharmacogenetic studies may be useful for clinicians to have a correct understanding of the phenomenon.

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Aripiprazole: from pharmacological profile to clinical use

Cited by 37 publications

References 84 publications

Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors

Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors

Classics in Chemical Neuroscience: Aripiprazole

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis

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