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.[5][7][19]
Side effects
Side effects may first appear several weeks after starting cariprazine.[6] The most prevalent side effects for cariprazine include akathisia and insomnia. 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, dizziness, vomiting, 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]
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-HT2Areceptor antagonists, cariprazine is a D2 and D3partial 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, 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]
Pharmacokinetics
Cariprazine has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic.[35] 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]
Cariprazine is also potentially useful as an add-on therapy in major depressive disorder.[37] 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.[38] Approval was granted by the FDA in December 2022 for cariprazine to be used as an adjunctive treatment for major depressive disorder.[39]
^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. PMID20093397. S2CID42933132.
^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. PMID24175719. S2CID23557344.
^ abNewman-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. PMID21394633. S2CID5835943.
^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.
^ abcGyertyán 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. PMID21767587. S2CID140205658.
^ abGründer 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. PMID20571978.
Kompleks piramida Senusret III, piramida Itakayt adalah yang ketiga dari kanan atas Itakayt merupakan seorang putri Mesir Kuno dari Dinasti ke-12, pada sekitar tahun 1800 SM. Ia terutama dikenal dari piramida kecilnya di samping Senusret III di Dahshur.[1] Ia bergelar putri raja dari tubuhnya, berkuasa, anggun dan dicintai. Piramida Piramidanya di sisi utara piramida raja berukuran sekitar 16.80 meter di dasar, dan dulunya juga tingginya 16.80 meter tingginya. Dibangun dari batu bata lum…
جائزة بلجيكا الكبرى 1981 السباق 5 من أصل 15 في بطولة العالم لسباقات الفورمولا واحد موسم 1981 السلسلة بطولة العالم لسباقات فورمولا 1 موسم 1981 البلد بلجيكا التاريخ 17 مايو 1981 مكان التنظيم بلجيكا طول المسار 4.011 كيلومتر (2.492 ميل) المسافة 216.594 كيلومتر، (134.585 ميل) حالة الطقس جاف أول …
الكتيبة الخاصة 71 شعار الكتيبة الخاصة 71 الدولة الأردن التأسيس 1973 - حتى الان الاسم الأصلي الكتيبة الخاصة 71 (الأردن) اسم آخر الوحدة الخاصة 2 القيادة رتبة القائد مقدم تعديل مصدري - تعديل القوات الأردنية الخاصة 71 هي فرقة مكافحة الإرهاب والعمليات الخاصة الأردنية والتي تحمي ا…
American politician For other people named Samuel Sawyer, see Samuel Sawyer (disambiguation). Samuel Locke SawyerMember of the U.S. House of Representativesfrom Missouri's 8th districtIn officeMarch 4, 1879 – March 3, 1881Preceded byBenjamin Joseph FranklinSucceeded byRobert T. Van Horn Personal detailsBorn(1813-11-27)November 27, 1813Mont Vernon, New Hampshire, USDiedMarch 29, 1890(1890-03-29) (aged 76)Independence, Missouri, USPolitical partyDemocraticProfessionlawy…
American politician Richard Howard Ichord Jr.Member of the U.S. House of Representativesfrom Missouri's 8th districtIn officeJanuary 3, 1961 – January 3, 1981Preceded byA. S. J. CarnahanSucceeded byR. Wendell BaileyMember of the Missouri House of RepresentativesIn office1952–1960 Personal detailsBorn(1926-06-27)June 27, 1926Licking, MissouriDiedDecember 25, 1992(1992-12-25) (aged 66)Houston, MissouriPolitical partyDemocraticAlma materUniversity of Missouri Richard H…
This article needs to be updated. Please help update this article to reflect recent events or newly available information. (May 2022) Cabbage growing in a Veggie unit[1] The Vegetable Production System (Veggie) is a plant growth system developed and used by NASA in outer space environments. The purpose of Veggie is to provide a self-sufficient and sustainable food source for astronauts as well as a means of recreation and relaxation through therapeutic gardening.[2] Veggie was de…
2022 song by IShowSpeed World CupSingle by IShowSpeedReleasedNovember 4, 2022 (2022-11-04)RecordedSeptember 21, 2022[1]StudioMetropolis (London)[1]GenreHip hop[2]Length4:16LabelWarnerSongwriter(s) Darren Watkins Jr. Ryan Wage Producer(s) IShowSpeed WageeBeats Joe Grasso IShowSpeed singles chronology Ronaldo (Sewey) (2022) World Cup (2022) Dogs (2023) Music videoWorld Cup on YouTubeAudio sampleIShowSpeed - World Cupfilehelp World Cup is a song by American Yo…
Perekacitraan 3D adalah proses grafik komputer 3D yang mengubah model 3D menjadi gambar 2D di komputer . Rekacitra 3D mungkin menyertakan efek fotorealistik atau gaya non-fotorealistik . Cara merekacitra Rekacitra 3D fotorealistik dari 6 kipas komputer menggunakan rendering radiositas, DOF, dan materi prosedural Perekacitraan adalah proses akhir pembuatan gambar atau animasi 2D sebenarnya dari adegan yang telah disiapkan. Hal ini dapat dibandingkan dengan mengambil foto atau merekam adegan setel…
Chemical compound ABT-418Identifiers IUPAC name 3-Methyl-5-[(2S)-1-methylpyrrolidin-2-yl]-1,2-oxazole CAS Number147402-53-7 NPubChem CID119380ChemSpider106627 YUNIIB9I6MZL7BWChEMBLChEMBL274525 YCompTox Dashboard (EPA)DTXSID10163711 Chemical and physical dataFormulaC9H14N2OMolar mass166.224 g·mol−13D model (JSmol)Interactive image SMILES CC1=NOC(=C1)[C@@H]2CCCN2C InChI InChI=1S/C9H14N2O/c1-7-6-9(12-10-7)8-4-3-5-11(8)2/h6,8H,3-5H2,1-2H3/t8-/m0/s1 YKey:ILLGYRJAYAAAEW-QMM…
Markas Banca Monte dei Paschi di Siena di Siena Bankir pedagang Cornelius Berenberg, anggota keluarga Berenberg. Kakeknya mendirikan Berenberg Bank tahun 1590 Daftar bank tertua ini mencakup lembaga-lembaga keuangan yang masih beroperasi dengan identitas hukum yang sama sejak didirikan sampai sekarang. Meski saat ini masih ada tujuh bank yang didirikan pada abad ke-17 dan 16 bank yang didirikan pada abad ke-18, daftar ini dipuncaki oleh dua bank yang masing-masing didirikan pada abad ke-15 dan 1…
Multi use stadium in Granada, Spain (opened 1995) Los CármenesUEFA Full nameNuevo Estadio de Los CármenesLocationCalle Pintor Manuel Maldonado, s/n. 18008 - Granada, SpainCoordinates37°9′11″N 3°35′45″W / 37.15306°N 3.59583°W / 37.15306; -3.59583OwnerAyuntamiento de GranadaCapacity19,336 [1]Field size105 × 68 mSurfaceGrassConstructionBuilt1993–1995Opened16 May 1995Renovated2011TenantsGranada CF (1995–present)CP Granada 74 (2002–2004)Granada Atl…
Questa voce sull'argomento politici burundesi è solo un abbozzo. Contribuisci a migliorarla secondo le convenzioni di Wikipedia. Melchior Ndadaye Presidente del BurundiDurata mandato10 luglio 1993 –21 ottobre 1993 PredecessorePierre Buyoya SuccessoreFrançois Ngeze Dati generaliPartito politicoFronte per la Democrazia in Burundi Melchior Ndadaye (Nyabihanga, 28 marzo 1953 – Bujumbura, 21 ottobre 1993) è stato un politico burundese. Quarto Presidente della repubblica…
This article is about the restaurant in New York City. For other uses, see Odeon. Restaurant in New York, United StatesThe OdeonThe restaurant's exterior in 2009Restaurant informationStreet address145 West BroadwayCityNew York CityStateNew YorkCountryUnited StatesCoordinates40°43′01″N 74°00′28″W / 40.716967°N 74.007841°W / 40.716967; -74.007841 The Odeon is a restaurant in New York City.[1] The restaurant opened in 1980, in space previously occupied by…
Disambiguazione – Divizia A rimanda qui. Se stai cercando altre competizioni rumene o moldave, vedi Divizia A (disambigua). SuperLiga RomânieiAltri nomiLiga I, Divizia A Sport Calcio TipoSquadre di club FederazioneFRF Paese Romania OrganizzatoreLPF TitoloCampione di Romania Cadenzaannuale Aperturaluglio Chiusuragiugno Partecipanti16 squadre Formulagirone all'italiana+poule scudetto o retrocessione Retrocessione inLiga II Sito Internetlpf.ro StoriaFondazione1909 Numero edizioni105…
2010 MTV Video Music Awards Tanggal September 12, 2010 Tempat Nokia Theatre Host Chelsea Handler[1] 2010 MTV Video Music Awards diadakan pada 12 September, 2010 di Nokia Theatre di Los Angeles, memberi penghargaan pada video musik terbaik tahun sebelumnya. Chelsea Handler menjadi host acara, perempuan pertama yang melakukan ini semenjak 1994 MTV Video Music Awards.[1] Keseluruhan, acara menangkan 11,4 juta penonton — penonton terbanyak sejak 2002[2] Nominasi Pemenang di…
CapucheCapuche d'un manteau d'hiver inuit.CaractéristiquesType Couvre-chefMatière lainecotonautre...modifier - modifier le code - modifier Wikidata La capuche[1] ou le capuchon[2] (parfois aussi nommé « capuce » chez les moines) est une coiffe conçue soit pour encadrer le visage, soit pour le cacher ; de fait, il a généralement une forme de voûte. La capuche fait souvent partie intégrante d'un vêtement, d'un manteau ou d'un imperméable (une sorte de grand bonnet qui co…
State Correctional Institution – RockviewLocationBenner Township, Centre County, Pennsylvania, USAOpened1915Managed byPennsylvania Department of Corrections SCI Rockview -- SCI Benner Township can be seen in the background SCI Rockview overhead view The State Correctional Institution – Rockview (SCI Rockview) is a Pennsylvania Department of Corrections prison located in Benner Township, Pennsylvania, 5 miles (8.0 km) away from Bellefonte.[1][2] A portion of the prison gr…
Greek civilization from c. 1200 BC to c. 600 AD The Parthenon, a temple dedicated to Athena, located on the Acropolis in Athens, is one of the most representative symbols of the culture and sophistication of the ancient Greeks. Part of a series on the History of Greece Neolithic Greece Pelasgians Greek Bronze Age Helladic Cycladic Minoan Mycenaean Greece 1750 BC–1050 BC Ancient Greece Greek Dark Ages 1050 BC–750 BC Archaic Greece 800 BC–480 BC Classical Greece 500 BC–323BC Hellenistic Gr…
South Slavic circle dance This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Kolo dance – news · newspapers · books · scholar · JSTOR (April 2014) (Learn how and when to remove this template message) Serbian kolo from Šumadija Serbian kolo from Timok Serbian kolo from Vranje Kolo (Serbian Cyrillic: Коло)…
