Subscribe to RSS
DOI: 10.1055/s-0038-1626332
Pharmakotherapie von ADHD
Biologische Grundlagen, Chancen und GrenzenPharmacotherapy of ADHDbiology, chances and limitationsPublication History
Publication Date:
18 January 2018 (online)

Zusammenfassung
Die verschiedenen Ausprägungen von ADHD lassen sich mit hoher Wahrscheinlichkeit auf Störungen der Reizübertragung im zentralen Nervensystem zurückführen. Diese benötigt im Bereich der Synapsen eine temporäre »chemische Brücke«, die von Neurotransmittern bei Bedarf – und nur dann – bereitgestellt und immer wieder neu auf- und abgebaut werden muss. Damit sind Angriffspunkte für eine medikamentöse Therapie von ADHD gegeben und definiert: Synthese, Freisetzung, Abbau, Aufnahme oder Transport solcher Neurotransmitter sollen so beeinflusst werden, dass eine »normale« Situation erreicht wird. Aktuelle Ergebnisse der Interaktion von Arzneistoffen mit Dopamin- bzw. Noradrenalinvermittelten Vorgängen werden vorgestellt und diskutiert.
Summary
There is now good evidence that ADHD is associated with disorders in the transmission of signals in the central nervous system. Synaptic signal transduction is realised by the formation of a temporary „chemical bridge” which is provided only on demand and constructed and destroyed incessantly. Hence, the targets and strategies to medicate ADHD are well defined: Synthesis, degradation, uptake or transport of neurotransmitters have to be affected with a view to approach the “normal” situation. Special emphasis will be placed on processes mediated by dopamine and noradrenaline.
-
Literatur
- 1 Barkley RA. Attention-deficit hyperactivity disorder. Sci Am 1998; 279: 66-71.
- 2 Barr CL, Wigg KG, Feng Y, Zai G, Malone M, Roberts W, Schachar R, Tannock R, Kennedy JL. Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor. Mol Psychiatry 2000; 05: 548-51.
- 3 Braus DF. Bilder der Seele. Kernspintomographie eröffnet erste Einblicke in die somatische Grundlage psychischer Prozesse. Medizinische Monatsschrift für Pharmazeuten 2003; 26: 45-51.
- 4 Curran S, Mill J, Tahir E, Kent L, Richards S, Gould A, Huckett L, Sharp J, Batten C, Fernando S, Ozbay F, Yazgan Y, Simonoff E, Thompson M, Taylor E. Asherson. Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 2001; 06: 425-8.
- 5 Darracq L, Blanc G, Glowinski J, Tassin JP. Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamine. J Neurosci 1998; 18: 2729-39.
- 6 Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR, Kidd KK, Flodman P, Spence MA, Schuck S, Swanson JM, Zhang YP, Moyzis RK. Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci USA 2002; 99: 309-14.
- 7 Faraone SV, Doyle AE, Mick E, Biederman J. Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 2001; 158: 1052-7.
- 8 Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL, Newbury DF, Crawford LR, Palmer CG, Woodward JA, Del’Homme M, Cantwell DP, Nelson SF, Monaco AP, Smalley SL. A genomewide scan for loci involved in attention-deficit/hyperactivity disorder. Am J Hum Genet 2002; 70: 1183-96.
- 9 Gainetdinov RR, Caron MG. An animal model of attention deficit hyperactivity disorder. Mol Med Today 2000; 06: 43-4.
- 10 Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 1999; 283: 397-401.
- 11 Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996; 379: 606-12.
- 12 Gonzalez MA, Pentikis HS, Anderl N, Benedict MF, DeCory HH, Dirksen SJ, Hatch SJ. Methylphenidate bioavailability from two extendedrelease formulations. Int J Clin Pharmacol Ther 2002; 40: 175-84.
- 13 Julien RM. Drogen und Psychopharmaka. Heidelberg, Berlin, Oxford: Spektrum Akademischer Verlag; 1997
- 14 Keating GM, McClellan K, Jarvis B. Methylphenidate (OROS formulation). CNS Drugs 2001; 15: 495-500.
- 15 Krause J, Ryffel-Rawak D. Therapie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter. Psycho 2000; 26: 209-23.
- 16 Kuczenski R, Segal DS. Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 2002; 22: 7264-71.
- 17 Marx J. How stimulant drugs may calm hyperactivity. Science 1999; 283: 306.
- 18 Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P. Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder. Am J Med Genet 2002; 114: 269-71.
- 19 Pauling L, Coryell C. The magnetic properties and structure of hemoglobin, oxyhemoglobin, and carbon monoxyhemoglobin. Proc Natl Acad Sci USA 1936; 22: 210-6.
- 20 Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, O’Donovan M, Owen M, Ollier W, Worthington J, Thapar A. Examining for association between candidate gene polymorphisms in the dopamine pathway and attentiondeficit hyperactivity disorder: a family-based study. Am J Med Genet 2001; 105: 464-70.
- 21 Petersen SE, Fox RT, Posner MI, Mintum M, Raichle ME. Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature 1988; 331: 585-9.
- 22 Posner MI, Raichle ME. Images of Mind. New York: W. H. Freeman; 1994
- 23 Roman T, Schmitz M, Polanczyk G, Eizirik M, Rohde LA, Hutz MH. Attention-deficit hyperactivity disorder: a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. Am J Med Genet 2001; 105: 471-8.
- 24 Spielewoy C, Roubert C, Hamon M, Nosten-Bertrand M, Betancur C, Giros B. Behavioural disturbances associated with hyperdopaminergia in dopamine-transporter knockout mice. Behav Pharmacol 2000; 11: 279-90.
- 25 Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder E, Wigal S. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder. Proof-ofconcept and proof-of-product studies. Arch Gen Psychiatry 2003; 60: 204-11.
- 26 Thapar A. Attention deficit hyperactivity disorder: unravelling the molecular genetics. Mol. Psychiatry 1998; 03: 370-2.
- 27 Velasco M, Contreras F, Cabezas GA, Bolivar A, Fouillioux C, Hernandez R. Dopaminergic receptors: a new antihypertensive mechanism. J Hypertens 2002; 20 (Suppl. 03) 55-8.
- 28 Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, Gatley SJ, Miller E, Hitzemann R, Ding YS, Logan J. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 2001; 21: 9414-8.
- 29 Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L, Ding Y, Gatley SJ, Gifford A, Franceschi D. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 2001; 21: RC121.
- 30 Weber P, Lütschg J. Methylphenidate treatment. Ped Neurology 2002; 26: 261-6.
- 31 Wilson MC. Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder. Neurosci Biobehav Rev 2000; 24: 51-7.