| Reference | 1. Ther Adv Psychopharmacol. 2017 Jan;7(1):29-41. doi: 10.1177/2045125316672136.
Epub 2016 Oct 17.
<br>
Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics
from the original dopamine stabilizer aripiprazole.
<br>
Frankel JS(1), Schwartz TL(2).
<br>
Author information: <br>
(1)Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
(2)Department of Psychiatry, SUNY Upstate Medical University, 750 E. Adams
Street, Syracuse, NY 13210, USA.
<br>
BACKGROUND: Brexpiprazole and cariprazine are the latest US Food and Drug
Administration approved atypical antipsychotics available in the United States.
Both function as partial agonists of the dopamine-2 receptor (D2R), a mechanism
of action shared with aripiprazole. However, all three differ in their affinities
for the D2R as well as for serotonin receptors (5-HTRs). This paper seeks to
delineate these pharmacodynamic and clinical differences amongst the three
dopamine partial agonist atypical antipsychotic drugs.<br>
METHODS: PubMed and clinicaltrials.gov searches were used to generate preclinical
and clinical evidence for review. Data derived from animal models and human
subjects were used to provide insight on clinical mechanisms and adverse effect
potentials. Clinical trial data were reviewed to compare clinical efficacy and
adverse effects.<br>
RESULTS: Efficacies among the three drugs are comparable for their shared
indications. Side-effect profile and underlying pharmacodynamic mechanism of
action for each drug may differ.<br>
CONCLUSION: Partial agonism of the D2R is a similarity of the three drugs
reviewed. Each drug varies in affinity for both the D2R and a diverse group of
5-HTRs, generating a distinct profile of clinical indications and adverse effects
for each.
<br>
2. Curr Pharm Des. 2016;22(33):5144-5162.
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The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment
of Psychiatric Disorders.
<br>
De Berardis D(1), Orsolini L, Iasevoli F, Prinzivalli E, de Bartolomeis A,
Serroni N, Mazza M, Valchera A, Fornaro M, Vecchiotti R, Carano A, Sepede G,
Vellante F, Matarazzo I, Pompili M, Perna G, Conti C, Segura-García C, Martinotti
G, Di Giannantonio M.
<br>
Author information: <br>
(1)National Health Service, Department of Mental Health, Psychiatric Service of
Diagnosis and Treatment, /G. Mazzini/ Hospital, p.zza Italia 1, 64100 Teramo,
Italy. [email protected].
<br>
Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism
of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism
of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in
late-stage clinical development (phase III clinical trials) in patients with
schizophrenia (S) and in patients with bipolar disorder (BD), as well as an
adjunctive treatment in patients with Major Depressive Disorder (MDD) and
drug-resistant MDD. Cariprazine has completed phase III trials for the acute
treatment of schizophrenia and bipolar mania, phase II trials for the bipolar
depression and MDD whilst it is undergoing phase III trials as an adjunct to
antidepressants. The present review aims at proving a comprehensive summary of
the current evidence on the safety, tolerability and efficacy of cariprazine in
the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A
systematic search was conducted on PubMed/Medline/ Scopus and the database on
Clinical Trials from inception until April 2015 by typing a set of specified
keywords. Available evidence seems to support cariprazine efficacy in the
treatment of cognitive and negative symptoms of schizophrenia. Preliminary
findings suggest its antimanic activity whilst it is still under investigation
its efficacy in the treatment of bipolar depression and MDD. Furthermore, the
available data seems not to allow judgements about its antipsychotic potential in
comparison with currently prescribed antipsychotics. Further studies should be
carried out to better investigate its pharmacodynamic and clinical potential,
particularly as alternative to current antipsychotic drugs.
<br>
3. Adv Ther. 2013 Feb;30(2):102-13. doi: 10.1007/s12325-013-0004-9. Epub 2013 Jan
28.
<br>
Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in
therapy.
<br>
Citrome L(1).
<br>
Author information: <br>
(1)Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, New
York, USA. [email protected]
<br>
Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist in
late-stage clinical development for the treatment of bipolar disorder
(manic/mixed and depressive episodes), as well as for schizophrenia, and as an
adjunctive agent for the treatment of major depressive disorder. Three phase 2 or
3, 3-week, randomized controlled trials in bipolar mania or mixed episodes have
been completed and reported as poster presentations or in press releases by the
manufacturer. Superiority over placebo on the Young Mania Rating Scale total
score was evidenced for daily doses of cariprazine 3-12 mg/day. In short-term
randomized controlled trials, cariprazine does not appear to adversely impact
metabolic variables, prolactin, or the electrocardiogram (ECG) QT interval. The
most commonly encountered adverse events in the mania trials were extrapyramidal
disorder, akathisia, insomnia, vomiting, restlessness, sedation, vision blurred,
and pain in extremity in the phase 2 trial where this was presented in a poster,
and akathisia, extrapyramidal disorder, tremor, dyspepsia, vomiting, dizziness,
diarrhea, somnolence, restlessness, and pyrexia for the phase 3 trial where this
was presented in a poster. With the exception of akathisia and extrapyramidal
disorder, the differences in incidence versus placebo for these events were
generally small. If approved by regulatory authorities, cariprazine would join
aripiprazole as the second dopamine receptor partial agonist antipsychotic
available for clinical use in persons with bipolar mania or mixed episodes.
Cariprazine differs from aripiprazole in terms of dopamine D3 receptor
selectivity. Further studies would be helpful to discern the distinguishing
features of cariprazine from other antimanic agents.
<br>
4. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi:
10.1517/17425255.2013.759211.
<br>
Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism,
clinical efficacy, safety, and tolerability.
<br>
Citrome L(1).
<br>
Author information: <br>
(1)New York Medical College, Valhalla, NY, USA. [email protected]
<br>
INTRODUCTION: Cariprazine is an atypical antipsychotic in clinical development
for the treatment of schizophrenia and bipolar mania/mixed episodes.
AREAS COVERED: The purpose of this review is to describe the chemistry,
pharmacodynamic profile, pharmacokinetics, and clinical profile of cariprazine.
EXPERT OPINION: Cariprazine is a dopamine D3-preferring D3/D2 receptor partial
agonist. Doses ≥ 1.5 mg/d yielded 69 – 75% D2/D3 receptor occupancy as measured
in positron emission tomography scans. Mean half-life for cariprazine was 2 – 5 d
over a dose range of 1.5 – 12.5 mg. Cariprazine produces two clinically relevant
metabolites: desmethyl-cariprazine and didesmethyl-cariprazine, the latter having
a longer half-life than cariprazine. Exposure to didesmethyl-cariprazine exceeded
that of the parent drug. Cariprazine is metabolized by CYP3A4 and to a lesser
extent by CYP2D6. The efficacy and safety of cariprazine have been so far
investigated only in a few short-term (unpublished) clinical trials; however,
three studies in schizophrenia and three studies in bipolar mania/mixed episodes
evidenced a statistically significant therapeutic effect compared to placebo for
cariprazine at doses ranging from 1.5 to 12 mg/d. There does not appear to be
clinically relevant adverse effects of cariprazine on metabolic variables.
Commonly encountered adverse events associated with cariprazine include insomnia,
extrapyramidal symptoms, akathisia, sedation, nausea, dizziness, and
constipation.
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