Nervenheilkunde 2004; 23(03): 171-173
DOI: 10.1055/s-0038-1626288
Forum Psychopharmacologicum
Schattauer GmbH

Aripiprazol – der prototypische Dopamin Serotonin-Systemstabilisator

Pharmakotherapie schizophrener PsychosenAripiprazole – the prototypical dopamine-serotonin systemstabilizer for the pharmacotherapy of schizophrenia
M. Koch
1   Abt. Neuropharmakologie, Institut für Hirnforschung, Universität Bremen, FB2
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
19. Januar 2018 (online)

Zusammenfassung

Tierexperimentelle Untersuchungen zeigen, dass Aripiprazol als partieller D2-Dopaminrezeptorund 5-HT1ASerotoninrezeptor-Agonist sowie als 5-HT2A-RezeptorAntagonist wirkt. Klinische Studien belegen, dass diese Substanz bei der Behandlung schizophrener Patienten mindestens so effektiv wie Haloperidol und Risperidon ist. Im Verträglichkeitsprofil zeigte sich eine Überlegenheit von Aripiprazol gegenüber den beiden anderen Antipsychotika. Aripiprazol kann aufgrund seiner neuartigen Pharmakologie und klinischen Wirksamkeit als prototypisches Antipsychotikum der Dopamin-SerotoninSystemstabilisatoren angesehen werden.

Summary

Aripiprazole is a D2-dopaminereceptorand a 5-HT1Aserotoninreceptor-agonist as well as a 5-HT2A-antagonist and has been characterised as a prototypical dopamineserotonin-system stabilizer. Clinical studies show that aripiprazole is at least as effective as haloperidol and risperidone in the treatment of schizophrenia, whilst its safety profile is superior to these other antipsychotics.

 
  • Literatur

  • 1 Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976; 192: 481-3.
  • 2 Meltzer HY, Stahl SM. The dopamine hypothesis of schizophrenia: A review. Schiz Bull 1976; 02: 19-76.
  • 3 Gründer G, Carlsson A, Wong DF. Mechanism of new antipsychotic medications. Arch Gen Psychiatry 2003; 60: 974-7.
  • 4 Fleischhacker WW. New developments in the pharmacotherapy of schizophrenia. J Neural Transm 2003; 64 Suppl. 105-17.
  • 5 Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, Morita S. 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy}-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther 1995; 274: 329-36.
  • 6 Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol 2002; 441: 137-40.
  • 7 McGavin JK, Goa KL. Aripiprazole. CNS Drugs 2002; 16: 779-86.
  • 8 Goodnick PJ, Jerry JM. Aripiprazole: profile on efficacy and safety. Expert Opin Pharmacother 2002; 03: 1773-81.
  • 9 Tamminga CA, Schaffer MH, Smith RC, Davis JM. Schizophrenic symptoms improve with apomorphine. Science 1978; 200: 567-8.
  • 10 Tamminga CA. Partial dopamine agonists in the treatment of psychosis. J Neural Transm 2002; 109: 411-20.
  • 11 Yamada S, Harano M, Yokoo H, Tanaka M. Antagonistic effects of OPC-14597, a novel antipsychotic drug, on quinpiroleand (-)-sulpiride-induced changes in evoked dopamine release in rat striatal slices. J Pharm Pharmacol 1997; 49: 206-8.
  • 12 Pulvirenti L, Koob GF. Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol Sci 1994; 15: 374-9.
  • 13 Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Yocca FD, Molinoff PB. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302: 381-9.
  • 14 Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth C, Schwarcz J-C, Everitt BJ, Sokoloff P. Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature 1999; 400: 371-5.
  • 15 Semba J, Watanabe A, Kito S, Toru M. Behavioural and neurochemical effects of OPC14597, a novel antipsychotic drug, on dopaminergic mechanisms in rat brain. Neuropharmacology 1995; 34: 785-91.
  • 16 Inoue A, Miki S, Seto M, Kikuchi T, Morita S, Ueda H, Misu Y, Nakata Y. Aripiprazole, a novel antipsychotic drug, inhibits quinpiroleevoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum. Eur J Pharmacol 1997; 321: 105-11.
  • 17 Inoue A, Seto M, Sugita S, Hide I, Hirose T, Koga N, Kikuchi T, Nakata Y. Differential effects on D2 dopamine receptor and prolactin gene expression by haloperidol and aripiprazole in the rat pituitary. Mol Brain Res 1998; 55: 285-92.
  • 18 Semba J, Sakai M, Miyoshi R, Mataga N, Fukamauchi F, Kito S. Differential expression of c-fos mRNA in rat prefrontal cortex, striatum, N. accumbens and lateral septum after typical and atypical antipsychotics: an in situ hybridization study. Neurochem Int 1996; 29: 435-42.
  • 19 Nakai S, Hirose T, Uwahodo Y, Imaoka T, Okazaki H, Miwa T, Nakai M, Yamada S, Dunn B, Burris KD. et al. Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone. Eur J Pharmacol 2003; 472: 89-97.
  • 20 Yokoi F, Grunder G, Biziere K, Stephane M, Dogan AS, Dannals RF, Ravert H, Suri A, Bramer S, Wong DF. 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 2002; 27: 248-59.
  • 21 Taylor DM. Aripiprazole: a review of its pharmacology and clinical use. Int J Clin Pract 2003; 57: 49-54.
  • 22 Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenitoon GG. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003; 166: 391-9.