Cariprazine

Last updated

Cariprazine
Cariprazine.svg
Cariprazine ball-and-stick model.png
Clinical data
Pronunciation /kəˈrɪprəˌziːn/
Trade names Vraylar, Reagila, Symvenu
Other namesRGH-188
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		By mouth
Drug class Atypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability High
Protein binding 91–97%
Metabolism Liver via CYP3A4 and to a lesser extent CYP2D6
Metabolites desmethylcariprazine, didesmethylcariprazine
Elimination half-life 2–4 days for parent drug, and 1–3 weeks for active metabolites
Excretion Urine (21%), bile
Identifiers
  • N'-[trans-4-[2-[4-(2,3-Dichlorophenyl)-1-piperazinyl]ethyl]cyclohexyl]-N,N-dimethylurea
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H32Cl2N4O
Molar mass 427.41 g·mol−1
3D model (JSmol)
  • CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(CC2)c2cccc(Cl)c2Cl)CC1
  • InChI=1S/C21H32Cl2N4O/c1-25(2)21(28)24-17-8-6-16(7-9-17)10-11-26-12-14-27(15-13-26)19-5-3-4-18(22)20(19)23/h3-5,16-17H,6-15H2,1-2H3,(H,24,28)/t16-,17- Yes check.svgY
  • Key:KPWSJANDNDDRMB-QAQDUYKDSA-N Yes check.svgY

Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, [8] which is used in the treatment of schizophrenia, bipolar mania, [9] bipolar depression, [10] and major depressive disorder. [6] It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors. [11] It is taken by mouth. [6] The most prevalent side effects include nausea, mild sedation, fatigue, and dizziness. At higher dosages, there is an increased risk for restlessness, insomnia, and tremors. [6]

Contents

Cariprazine was approved for medical use in the United States in September 2015. [12] It was approved as a generic medication in 2022, [13] but is covered by patents until 2029. [14]

Medical uses

Cariprazine is used to treat patients with schizophrenia and manic, depressive, or mixed episodes associated with bipolar I disorder. In the United States it is approved for schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and treatment of depressive episodes associated with bipolar I disorder (bipolar depression). [15] [6] [16]

Cariprazine consistently improved depressive symptoms across a spectrum of patients with bipolar I depression. [17] [18] In Australia, the United Kingdom, and the European Union it is approved only for treating schizophrenia. [4] [7] [19]

Side effects

Side effects may first appear several weeks after starting cariprazine. [6] Cariprazine does not appear to impact prolactin levels, and unlike many other antipsychotics, does not increase the QT interval on the electrocardiogram (ECG). In short term clinical trials, extrapyramidal effects, sedation, akathisia, nausea, headache, dizziness, vomiting, insomnia, anxiety, and constipation were observed. One review characterized the frequency of these events as "not greatly different from that seen in patient treated with placebo" [20] but a second called the incidence of movement-related disorders "rather high". [21] [22]

Regarding these side effects, the label of cariprazine states, "The possibility of lenticular changes or cataracts cannot be excluded at this time." [6]

Because cariprazine and its active metabolites have long half-lives, many healthcare professionals monitor for adverse effects up to several weeks after starting cariprazine. A longer monitoring period is also indicated for dosage changes, whether they represent an increase or a decrease, because elimination may take several weeks. [23]

Pharmacology

Pharmacodynamics

Cariprazine [24] [15] [25] [26]
SiteKi (nM)IA (%)Action
5-HT1A 2.6~40%Partial agonist
5-HT2A 18.8Antagonist
5-HT2B 0.58Antagonist
5-HT2C 134Inverse agonist
5-HT7 111Antagonist
α1A 155Antagonist
D2L 0.49~30%Partial agonist
D2S 0.69~30%Partial agonist
D3 0.085~70%Partial agonist
H1 23.2Antagonist
mACh Tooltip Muscarinic acetylcholine receptor>1,000Antagonist
The smaller the Ki value, the more strongly the drug binds to the site. IA=intrinsic activity.

Unlike many antipsychotics that are D2 and 5-HT2A receptor antagonists, cariprazine is a D2 and D3 partial agonist. It also has a higher affinity for D3 receptors. The D2 and D3 receptors are important targets for the treatment of schizophrenia, because the overstimulation of dopamine receptors has been implicated as a possible cause of schizophrenia. [27] Cariprazine acts to inhibit overstimulated dopamine receptors (acting as an antagonist) and stimulate the same receptors when the endogenous dopamine levels are low. Cariprazine's high selectivity towards D3 receptors could prove to reduce side effects associated with the other antipsychotic drugs, because D3 receptors are mainly located in the ventral striatum and would not incur the same motor side effects (extrapyramidal symptoms) as drugs that act on dorsal striatum dopamine receptors. [28] Cariprazine also acts on 5-HT1A receptors, though the affinity is considerably lower than the affinity to dopamine receptors (seen in monkey and rat brain studies). [28] [29] In the same studies, cariprazine has been noted to produce pro-cognitive effects, the mechanisms of which are currently under investigation. An example of pro-cognitive effects occurred in pre-clinical trials with rats: rats with cariprazine performed better in a scopolamine-induced learning impairment paradigm in a water labyrinth test. This may be due to the selective antagonist nature of D3 receptors, though further studies need to be conducted. [28] This result could be very useful for schizophrenia, as one of the symptoms includes cognitive deficits.

Cariprazine has partial agonist as well as antagonist properties depending on the endogenous dopamine levels. When endogenous dopamine levels are high (as is hypothesized in schizophrenic patients), cariprazine acts as an antagonist by blocking dopamine receptors. When endogenous dopamine levels are low, cariprazine acts more as an agonist, increasing dopamine receptor activity. [20] In monkey studies, the administration of increasing doses of cariprazine resulted in a dose-dependent and saturable reduction of specific binding. At the highest dose (300 μg/kg), the D2/D3 receptors were 94% occupied, while at the lowest dose (1 μg/kg), receptors were 5% occupied. [29] Dopamine D2 and D3 receptor occupancy in humans has been summarized as, "In healthy volunteers, single-dose cariprazine of 0.5 mg occupied up to 12% of striatal D2/D3 receptors, while striatal D2/D3 occupancy after multiple dosing up to cariprazine 1.0 mg/d ranged from 63 to 79% [39]. In an open-label, fixed-dose, 2-week trial in eight males with schizophrenia, PET scans of dorsal striatal regions (caudate nucleus and putamen) and ventral striatum (nucleus accumbens) showed maximum occupancy (‡ 90%) at a 3-mg target dose of cariprazine following 14 d of treatment [40,41]. After 14 d of cariprazine 1.5 mg/d, receptor occupancy was 69% in the caudate nucleus, 69% in the nucleus accumbens, and 75% in the putamen". [20]

Mechanism of cariprazine action as antagonist or agonist. Cariprazine mechanism.png
Mechanism of cariprazine action as antagonist or agonist.

Cariprazine, as well as other third generation antipsychotics, possesses a lower chance of exacerbating extrapyramidal symptoms. However the ability to induce akathasia remains relatively high. This may be mediated through a lack of anticholinergic effects (as agents of this class are sometimes used to treat akathisia), as well as a lack of a balanced dopaminergic(D2)/serotonergic(5-HT2A) ratio (compared to the second generation antipsychotics serving a more nuanced profile in this regard)[ clarify ]. [30] [31] [32] Moreover, partial agonists, through their limited response triggering, ironically often have the tendency to occupy near all targeted receptors at relatively low dosages of the drug. An extreme example is aripiprazole with an average occupancy of 70% (D2) at a 2 mg dose, well below its usual antipsychotic dosage (the often cited threshold of occupancy for an antipsychotic effect is 70%). This could be another reason for akathasia from partial agonists. [33] [34]

This Partial agonist activity induces, considered through two depicted schematas in pharmacology (either in determing their intrinsic value of activity making up the proportions of how much of a dose of this molecule binds to postsynaptic (dopamine)receptors to inactivate further exacerbating signalling through agonists with locking the receptor making it unavailable for other molecules and binding to the presynaptic site at autoreceptors in the synaptic cleft which triggers the transmitting with agonistic behaviour, or, binding indipendently to the site in the synaptic cleft inducing a certain response in relative to its agonist maximum potential to activate its relative receptor, then, depicted as percentage of intrinsic avtivity for this specific partial agonist) but with both needed to express just a "half-maximal response" (caught statistically in EC-responsecurves in a response-inhibited curve for maximal activation in graphes stretched on their longitudes, which it's due to their effect enabling tendency in time) to be able to compete sucessfully, relative to their dependent natural agonists (in case of antipsychotics dopamine) at full partialagonist concentrations where it happens to turn out luckily that atypical antipsychotics working as partialagonists (or the so-called third generation; e.g. aripiprazole, cariprazine and brexpiprazole) demonstrating near full "occupation" or concentration of thei in the brain where then this idea of competing and inhibiting dopamin tends to work out (because the alone-giveable possibility what a neuroleptic per definition has to be to called by this name, needs to have an antipsychotic (or positive symptomps erasing effect), e.g. being moodstabilizing), where without the pharmacologic term of a partialagonist would just work out to exacerbate and activate receptors by an unsatisfying concentration of it in the brain. [35] [36] [37] [38]

Pharmacokinetics

Cariprazine has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic. [39] In rats, the oral bioavailability was 52% (with a dose of 1 mg/kg). [22]

Cariprazine is metabolized primarily by the cytochrome P450 3A4 isoenzyme (CYP3A4), with some minor metabolism by CYP2D6. Cariprazine does not induce the production of CYP3A4 or CYP1A2 in the liver, and weakly, competitively inhibits CYP2D6 and CYP3A4. [15]

Research

Positive Phase III study results were published for schizophrenia and mania in early 2012, and for bipolar disorder I depression from a Phase II trial in 2015. [40] [39]

Cariprazine is also potentially useful as an add-on therapy in major depressive disorder. [41] It is being developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the US, Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela). In February 2022, AbbVie requested approval by the US Food and Drug Administration (FDA) for adjunctive treatment for major depressive disorder. [42] Approval was granted by the FDA in December 2022 for cariprazine to be used as an adjunctive treatment for major depressive disorder. [43]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its tranquillizing effects, the benefits of such use may not outweigh the risk of undesirable side effects. It is taken orally.

<span class="mw-page-title-main">Ziprasidone</span> Antipsychotic medication

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomiting and as an appetite stimulant. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, tic disorders. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.

<span class="mw-page-title-main">Pramipexole</span> Dopamine agonist medication

Pramipexole, sold under the brand Mirapex among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.

<span class="mw-page-title-main">Dopamine agonist</span> Compound that activates dopamine receptors

A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.

<span class="mw-page-title-main">Iloperidone</span> Atypical antipsychotic medication

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia and bipolar I disorder.

Dopamine receptor D<sub>2</sub> Main receptor for most antipsychotic drugs

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon H. Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar depression. It is taken by mouth.

<span class="mw-page-title-main">Roxindole</span> Dopaminergic & serotonergic drug developed for schizophrenia treatment

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.

<span class="mw-page-title-main">Desmethylclozapine</span> Active metabolite of the drug clozapine

N-Desmethylclozapine (NDMC), or norclozapine, is a major active metabolite of the atypical antipsychotic drug clozapine.

<span class="mw-page-title-main">F-15063</span> Chemical compound

F-15,063 is an orally active potential antipsychotic, and an antagonist at the D2/D3 receptors, partial agonist at the D4 receptor, and agonist at the 5-HT1A receptors. It has greater efficacy at the 5-HT1A receptors than other antipsychotics, such as clozapine, aripiprazole, and ziprasidone. This greater efficacy may lead to enhanced antipsychotic properties, as antipsychotics that lack 5-HT1A affinity are associated with increased risk of extrapyramidal symptoms, and lack of activity against the negative symptoms of schizophrenia.

<span class="mw-page-title-main">Brexpiprazole</span> Atypical antipsychotic

Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.

<span class="mw-page-title-main">Brilaroxazine</span> Experimental atypical antipsycotic

Brilaroxazine, also known as oxaripiprazole, is an investigational atypical antipsychotic which is under development by Reviva Pharmaceuticals for the treatment of neuropsychiatric and inflammatory disorders. It has currently completed the first of two phase III clinical trials for schizophrenia. Reviva Pharmaceuticals also intends to investigate brilaroxazine for the treatment of bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder (ADHD), irritability in autism, tics, psychosis/agitation associated with Alzheimer's disease, Parkinson's disease psychosis, as well as the inflammatory disorders pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), and psoriasis. The FDA granted brilaroxazine orphan drug designation for the treatment of PAH and IPF.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

References

  1. 1 2 "AusPAR: Cariprazine hydrochloride". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 4 January 2023. Retrieved 18 April 2023.
  2. ↑ "Vraylar Product information". Health Canada . 25 April 2012. Archived from the original on 29 June 2022. Retrieved 29 June 2022.
  3. ↑ "Summary Basis of Decision - Vraylar". Health Canada. 26 August 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022.
  4. 1 2 "Reagila 1.5 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 9 August 2018. Archived from the original on 21 October 2020. Retrieved 20 October 2020.
  5. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  6. 1 2 3 4 5 6 7 "Vraylar- cariprazine capsule, gelatin coated Vraylar- cariprazine kit". DailyMed. 18 May 2019. Archived from the original on 24 October 2020. Retrieved 20 October 2020.
  7. 1 2 "Reagila EPAR". European Medicines Agency (EMA). 18 September 2017. Archived from the original on 24 October 2020. Retrieved 20 October 2020.
  8. ↑ Laszlovszky I, Barabássy Á, Németh G (July 2021). "Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety". Advances in Therapy. 38 (7): 3652–3673. doi:10.1007/s12325-021-01797-5. PMC   8279990 . PMID   34091867.
  9. ↑ Agai-Csongor E, Domány G, Nógrádi K, Galambos J, Vágó I, Keserű GM, et al. (May 2012). "Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors". Bioorganic & Medicinal Chemistry Letters. 22 (10): 3437–3440. doi:10.1016/j.bmcl.2012.03.104. PMID   22537450.
  10. ↑ Earley W, Burgess MV, Rekeda L, Dickinson R, Szatmári B, Németh G, et al. (June 2019). "Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study". The American Journal of Psychiatry. 176 (6): 439–448. doi: 10.1176/appi.ajp.2018.18070824 . PMID   30845817.
  11. ↑ Kiss B, Horváth A, Némethy Z, Schmidt E, Laszlovszky I, Bugovics G, et al. (April 2010). "Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile". The Journal of Pharmacology and Experimental Therapeutics. 333 (1): 328–340. doi:10.1124/jpet.109.160432. PMID   20093397. S2CID   42933132.
  12. ↑ "FDA approves new drug to treat schizophrenia and bipolar disorder" (Press release). U.S. Food and Drug Administration. 17 September 2015. Archived from the original on 26 January 2018. Retrieved 16 December 2019.
  13. ↑ "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  14. ↑ "Generic Vraylar Availability". Drugs.com. 9 March 2023. Archived from the original on 26 March 2023. Retrieved 26 March 2023.
  15. 1 2 3 Citrome L (February 2013). "Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability". Expert Opinion on Drug Metabolism & Toxicology. 9 (2): 193–206. doi:10.1517/17425255.2013.759211. PMID   23320989. S2CID   36750662.
  16. ↑ Do A, Keramatian K, Schaffer A, Yatham L (2021). "Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials". Frontiers in Psychiatry. 12: 769897. doi: 10.3389/fpsyt.2021.769897 . PMC   8712443 . PMID   34970166.
  17. ↑ Patel M, Jain R, Tohen M, Maletic V, Earley WR, Yatham LN (March 2021). "Efficacy of cariprazine in bipolar I depression across patient characteristics: a post hoc analysis of pooled randomized, placebo-controlled studies". International Clinical Psychopharmacology. 36 (2): 76–83. doi:10.1097/YIC.0000000000000344. PMC   7846289 . PMID   33230026.
  18. ↑ Tohen M (2021). "Cariprazine as a Treatment Option for Depressive Episodes Associated with Bipolar 1 Disorder in Adults: An Evidence-Based Review of Recent Data". Drug Design, Development and Therapy. 15: 2005–2012. doi: 10.2147/DDDT.S240860 . PMC   8126799 . PMID   34012253.
  19. ↑ "Cariprazine hydrochloride for schizophrenia". Australian Prescriber. 44 (5): 170–171. October 2021. doi:10.18773/austprescr.2021.047. PMC   8542486 . PMID   34728883.
  20. 1 2 3 Citrome L (February 2013). "Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy". Advances in Therapy. 30 (2): 114–126. doi: 10.1007/s12325-013-0006-7 . PMID   23361833.
  21. ↑ Veselinović T, Paulzen M, Gründer G (November 2013). "Cariprazine, a new, orally active dopamine D2/3 receptor partial agonist for the treatment of schizophrenia, bipolar mania and depression". Expert Review of Neurotherapeutics. 13 (11): 1141–1159. doi:10.1586/14737175.2013.853448. PMID   24175719. S2CID   23557344.
  22. 1 2 Newman-Tancredi A, Kleven MS (August 2011). "Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties". Psychopharmacology. 216 (4): 451–473. doi:10.1007/s00213-011-2247-y. PMID   21394633. S2CID   5835943.
  23. ↑ Stahl SM, ed. (2020). "Cariprazine". Prescriber's Guide: Stahl's Essential Psychopharmacology (7th ed.). Cambridge: Cambridge University Press. pp. 137–146. doi:10.1017/9781108921275.024. ISBN   978-1-108-92601-0. Archived from the original on 18 May 2024. Retrieved 11 October 2022.
  24. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 22 May 2021. Retrieved 14 August 2017.
  25. ↑ Herman A, El Mansari M, Adham N, Kiss B, Farkas B, Blier P (December 2018). "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". Molecular Pharmacology. 94 (6): 1363–1370. doi: 10.1124/mol.118.113290 . PMID   30322874. S2CID   53096758.
  26. ↑ Mohr P, Masopust J, Kopeček M (25 January 2022). "Dopamine Receptor Partial Agonists: Do They Differ in Their Clinical Efficacy?". Frontiers in Psychiatry. 12: 781946. doi: 10.3389/fpsyt.2021.781946 . PMC   8821167 . PMID   35145438.
  27. ↑ Seeman P, Kapur S (July 2000). "Schizophrenia: more dopamine, more D2 receptors". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7673–7675. Bibcode:2000PNAS...97.7673S. doi: 10.1073/pnas.97.14.7673 . PMC   33999 . PMID   10884398.
  28. 1 2 3 Gyertyán I, Kiss B, Sághy K, Laszy J, Szabó G, Szabados T, et al. (November 2011). "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". Neurochemistry International. 59 (6): 925–935. doi:10.1016/j.neuint.2011.07.002. PMID   21767587. S2CID   140205658.
  29. 1 2 Seneca N, Finnema SJ, Laszlovszky I, Kiss B, Horváth A, Pásztor G, et al. (December 2011). "Occupancy of dopamine D₂ and D₃ and serotonin 5-HT₁A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography". Psychopharmacology. 218 (3): 579–587. doi:10.1007/s00213-011-2343-z. PMC   3210913 . PMID   21625907.
  30. ↑ Jethwa KD (September 2015). "Pharmacological management of antipsychotic-induced akathisia: an update and treatment algorithm". BJPsych Advances. 21 (5): 342–344. doi: 10.1192/apt.bp.114.013797 . S2CID   146670706.
  31. ↑ Citrome L, Yatham LN, Patel MD, Barabássy Á, Hankinson A, Earley WR (June 2021). "Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression". Journal of Affective Disorders. 288: 191–198. doi: 10.1016/j.jad.2021.03.076 . PMID   33915374. S2CID   233462432.
  32. ↑ Cohen LJ (1994). "Risperidone". Pharmacotherapy. 14 (3): 253–65. doi:10.1002/j.1875-9114.1994.tb02819.x. PMID   7524043.
  33. ↑ "Full agonists, partial agonists and inverse agonists | Deranged Physiology". Archived from the original on 14 February 2023. Retrieved 21 February 2023.
  34. ↑ Yokoi F, Gründer G, Biziere K, Stephane M, Dogan AS, Dannals RF, et al. (August 2002). "Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride". Neuropsychopharmacology. 27 (2): 248–259. doi: 10.1016/S0893-133X(02)00304-4 . PMID   12093598. S2CID   26101524.
  35. ↑ Ribeiro ELA, Vieira MEB (2018). "Efficacy and safety of aripiprazole for the treatment of schizophrenia: An overview of systematic reviews". European Journal of Clinical Pharmacology. 74 (10): 1215–1233. doi:10.1007/s00228-018-2498-1. PMID   29905899.
  36. ↑ Tuplin EW, Holahan MR (2017). "Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity". Current Neuropharmacology. 15 (8): 1192–1207. doi:10.2174/1570159X15666170413115754. PMC   5725548 . PMID   28412910.
  37. ↑ Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, et al. (2002). "Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors". The Journal of Pharmacology and Experimental Therapeutics. 302 (1): 381–389. doi:10.1124/jpet.102.033175. PMID   12065741.
  38. ↑ "Partial agonist".
  39. 1 2 Gründer G (July 2010). "Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression". Current Opinion in Investigational Drugs. 11 (7): 823–832. PMID   20571978.
  40. ↑ Durgam S, Earley W, Lipschitz A, Guo H, Laszlovszky I, Németh G, et al. (March 2016). "An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression". The American Journal of Psychiatry. 173 (3): 271–281. doi: 10.1176/appi.ajp.2015.15020164 . PMID   26541814.
  41. ↑ "Safety and Efficacy of Cariprazine As Adjunctive Therapy In Major Depressive Disorder". ClinicalTrials.gov. U.S. National Library of Medicine. Archived from the original on 6 December 2018. Retrieved 6 December 2018.
  42. ↑ "AbbVie Submits Supplemental New Drug Application to U.S. FDA for cariprazine (major depressive disorder) for the Adjunctive Treatment of Major Depressive Disorder". AbbVie (Press release). Archived from the original on 16 October 2022. Retrieved 11 October 2022.
  43. ↑ "U.S. FDA Approves Vraylar (cariprazine) as an Adjunctive Treatment for Major Depressive Disorder" (Press release). AbbVie. 16 December 2022. Archived from the original on 4 January 2023. Retrieved 3 January 2023– via PR Newswire.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.