Aripiprazole

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Structural formula
Structural formula
General
Non-proprietary name Aripiprazole
other names

7- {4- [4- (2,3-dichlorophenyl) piperazin-1-yl] -butoxy} -3,4-dihydro-1 H -quinolin-2-one ( IUPAC )

Molecular formula C 23 H 27 Cl 2 N 3 O 2
External identifiers / databases
CAS number 129722-12-9
EC number 603-355-5
ECHA InfoCard 100.112.532
PubChem 60795
ChemSpider 54790
DrugBank DB01238
Wikidata Q411188
Drug information
ATC code

N05 AX12

Drug class
Mechanism of action
  • D 2 receptor partial agonist
  • 5HT 1A receptor partial agonist
  • 5HT 2A receptor antagonist
properties
Molar mass 448.39 g · mol -1
Physical state

firmly

Melting point

139.0-139.5 ° C

solubility

0.02 mg l −1 in water

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 301
P: 264-270-301 + 312 + 330-501
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Aripiprazole is a drug from the group of atypical neuroleptics and is indicated for the treatment of schizophrenia in adults and adolescents from 15 years of age, for the treatment of moderate to severe manic phases of bipolar I disorder in adults and adolescents from 13 years of age and for the prevention of new ones manic episodes in adults. Under the trade name Abilify , it was approved throughout Europe in 2004 in the form of tablets, orodispersible tablets, injection solutions and oral solutions. Marketing authorization holder is Ōtsuka Pharmaceutical Co., Ltd. Abilify is one of the " blockbuster drugs" (2010 sales over 7 billion dollars).

Pharmacodynamic and pharmacokinetic properties

Aripiprazole is a functionally selective ligand on the dopamine D 2 receptor . It seems at this receptor as a partial agonist on the G protein Gαi / o , while on the Gβγ - signaling a robust antagonist acts. At the 5-HT 2A receptor, aripiprazole acts as a pure antagonist. In addition, it activates the 5-HT 1A receptor as a partial agonist.

Aripiprazole has a half-life of 60–80 hours. A maximum plasma concentration is reached after about three to five hours.

The agonistic effect is useful in the case of a relative dopamine deficiency in the CNS : The approximately 30% agonism is said to be effective in the frontal lobe, for example.

With increased neurotransmission to D 2 -receptors, as it is assumed for schizophrenia (hypothesis: oversupply of dopamine in the limbic system, among other things responsible for the development of emotions), one uses the antagonistic effect on this receptor (" dopamine hypothesis ").

Due to its partial agonism, aripiprazole is also known as a representative of the third generation of neuroleptics.

Clinical effect

Despite the novel mechanism of action, aripiprazole is no better than previous neuroleptics in schizophrenia, and only a few data from clinical studies are available for public assessment.

unwanted effects

The undesirable effects include extrapyramidal motor disorders , which, however, only occur half as often as with haloperidol treatment. The frequency of tardive dyskinesias cannot yet be assessed. It is assumed that there is a lower risk with atypicals compared to older preparations, but this has not been proven.

Worsening of psychotic symptoms has been reported in isolated cases . This disruptive effect is also associated with the special mechanism of action of aripiprazole.

The following side effects can also occur:

In elderly patients with dementia , aripiprazole increases mortality ; therefore it should not be prescribed to these patients.

Aripiprazole with sensor

In November 2017, Otsuka Pharmaceutical received approval from the US Food and Drug Administration (FDA) for aripiprazole with a sensor: Abilify MyCite . The tablets contain an embedded sensor that records that the medication has been taken and has dissolved in the stomach. The sensor sends a message to a wearable patch when digestion occurs. The patch transmits the information to a smartphone, for example, so that the patient can follow the intake on a digital medium. The FDA emphasizes that Abilify MyCite's ability to improve patient compliance has not been demonstrated. The sensor technology comes from Proteus Digital Health .

See also

Web links

Individual evidence

  1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 129, ISBN 978-0-911910-00-1 .
  2. ↑ K. Takács-Novák, M. Urac, P. Horváth, G. Völgyi, BD Anderson, A. Avdeef: Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi's Facilitated Dissolution Method. A validation study. In Eur. J. Pharm. Sci. 106 (2017) pp. 133-144, doi : 10.1016 / j.ejps.2017.05.064 .
  3. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 2 (1H) -quinolinones, 7- [4- [4- (2,3-dichlorophenyl) -1-piperazinyl] butoxy] -3,4-dihydro- in the Classification and derived from a self-classification by the distributor is shown Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 17, 2019.
  4. ↑ Entry on aripiprazole at TCI Europe, accessed on February 16, 2020.
  5. ↑ apotheken-umschau.de: Abilify 5mg tablets ( Memento of the original from August 8, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.apotheken-umschau.de
  6. ↑ TF Brust, MPHayes, DL Roman, VJ Watts: New functional activity of aripiprazole revealed: Robust antagonism of D2 dopamine receptor-stimulated Gβγ signaling . In: Biochem. Pharmacol. . 93, No. 1, 2015, pp. 85–91. doi : 10.1016 / j.bcp.2014.10.014 . PMID 25449598 . PMC 4276521 (free full text).
  7. ↑ a b O. Benkert, Hanns Hippius: Compendium of Psychiatric Pharmacotherapy . 12th, completely revised and updated edition. Berlin, Germany, ISBN 978-3-662-57334-1 ( limited preview in Google book search).
  8. ^ AD Stark, S. Jordan, KA Allers, RL Bertekap, R. Chen, T. Mistry Kannan, TF Molski, FD Yocca, T. Sharp, T. Kikuchi, KD Burris: Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies . In: Psychopharmacology (Berl.) . 190, No. 3, 2007, pp. 373-82. doi : 10.1007 / s00213-006-0621-y . PMID 17242925 .
  9. ↑ A. de Bartolomeis, C. Tomasetti, F. Iasevoli: Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism . In: CNS Drugs . 29, No. 9, 2015, pp. 773-799. doi : 10.1007 / s40263-015-0278-3 . PMID 26346901 . PMC 4602118 (free full text).
  10. ↑ HG El-Sayeh et al. (2006): Aripiprazole for schizophrenia. Systematic review. Br J Psychiatry. 189: pp. 102-108, PMID 16880478 .
  11. ^ Swiss specialist information on aripiprazole.
  12. ↑ DS Fernald et al. (2006): Aripiprazole in chronic schizophrenia: experiences in daily practice . Acta Psychiatr Scand. 114 (4): p. 294, PMID 16968370 .
  13. ↑ S. Ramaswamy et al. (2004): Aripiprazole possibly worsens psychosis. Int Clin Psychopharmacol . 19 (1): pp. 45-48, PMID 15101571 .
  14. ↑ Hypersexuality under aripiprazole (Abilify®) - Deutsches Ärzteblatt 103, issue 51–52 of December 25, 2006.
  15. ↑ Bulbena-Cabré A, Bulbena A: Aripiprazole -Induced Hypersexuality. , Prim Care Companion CNS Disord. 2016 Dec 29; 18 (6), PMID 28033456
  16. ↑ DJ Muzina, C. Momah, JM Eudicone, A. Pikalov, RD McQuade, RN Marcus, R. Sanchez, BX Carlson: Aripiprazole monotherapy in patients with rapid-cycling bipolar I disorder: an analysis from a long-term, double- blind, placebo-controlled study . In: Int. J. Clin. Pract. . 62, No. 5, 2008, pp. 679-87. doi : 10.1111 / j.1742-1241.2008.01735.x . PMID 18373615 . PMC 2324208 (free full text).
  17. ↑ Specialist information for Abilify ® from the Swiss drug compendium .
  18. ↑ J. Brunelle et al. (2007): Aripiprazole and neuroleptic malignant syndrome. J Clin Psychopharmacol . 27 (2): pp. 212-214, PMID 17414250 .
  19. ↑ PT Tseng et al .: Atypical neuroleptic malignant syndrome in patients treated with aripiprazole and clozapine: a case-series study and short review. In: International journal of psychiatry in medicine. Volume 49, number 1, 2015, pp. 35-43, doi : 10.2190 / PM.49.1.c , PMID 25838319 (review).
  20. ↑ a b Package insert Abilify 10 mg tablets ( Memento of the original from October 6, 2014 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.apotheken-umschau.de
  21. ↑ Rote Liste® Service GmbH: Abilify 5 mg / -10 mg / -15 mg / 30 mg tablets - patient information service. Retrieved June 19, 2020 .
  22. ↑ ABILIFY - Prescription information. (US) as of October 2006.
  23. ↑ FDA approves pill with sensor that digitally tracks if patients have ingested their medication , PM FDA of November 13, 2017, accessed on November 27, 2017