Neuere Aspekte zur Wirkungsweise von Methylphenidat

Zusammenfassung

Bislang wurde angenommen, dass Methyl-phenidat (MPH) seine Wirkung im Wesentlichen über den Dopaminstoffwechsel entfaltet; die nachgewiesene Blockade der Dopamintransporter im Striatum durch MPH führt zu einer Erhöhung des Dopamins im synaptischen Spalt. Mittlerweile liegen Befunde vor, wonach MPH auch die Noradrenalintransporter blockiert, somit gleichfalls auf Dopamin- und Noradrenalinstoffwechsel vor allem im Frontalhirn einwirkt. Weitere Befunde zeigen eine Beeinflussung von Azetylcholin und Histamin durch MPH. Im Gegensatz zu Am-phetamin, Methamphetamin, Kokain und MDMA (Ecstasy) scheint MPH keinen nennenswerten Einfluss auf den Serotonintransporter zu haben.

Summary

Until now it has been assumed, that methylphenidate (MPH) exerts its action preferably on dopamine metabolism; a blockade of striatal dopamine transporter by MPH with the consequence of an elevation of dopamine in the synaptic cleft has been described. Meanwhile results have been presented, whereupon MPH also blocks the norepinephrine transporter, thus influencing dopamine and norepinephrine metabolism especially in frontal regions. Further investigations showed an influence of MPH also on acetylcholine and histamine. In contrast to amphetamine, methamphetamine, cocaine and MDMA (Ecstasy), MPH seems not to effect the serotonine transporter in a remarkable extent.

Schlüsselwörter

Methylphenidat - Wirkmechanismus - Neurotransmitter

Keywords

Methylphenidate - mode of action - neurotransmitter

• Literatur

• 1 Arakawa R. et al. Quantitative analysis of norepinephrine transporter in the human brain using PET with (S,S)-18F-FMeNER-D2. J Nucl Med 2008; 49: 1270-1276.
• 2 Berridge CW. et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 2006; 60: 1111-1120.
• 3 Brown TE. Attention-deficit disorders and comorbidities in children, adolescents, and adults. Washington, London: American Psychiatric Press; 2000
• 4 Drouin C, Page M, Waterhouse B. Methylphenidate enhances noradrenergic transmission and suppresses midand long-latency sensory responses in the primary somatosensory cortex of awake rats. J Neurophysiol 2006; 96: 622-632.
• 5 Gerlach M. Pharmakologie von Methylphenidat. In: Schulte-Markwort M, Warnke A. (Hrsg). Methylphenidat. Stuttgart: Thieme; 2004
• 6 Han DD, Gu HH. Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 2006; 06: 6.
• 7 Horner WE. et al. Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex. Eur J Pharmacol 2007; 558: 96-97.
• 8 Ishimatsu M. et al. Effects of methylphenidate on the membrane potential and current in neurons of the rat locus coeruleus. J Neurophysiol 2002; 87: 1206-1212.
• 9 Kim CH. et al. A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder. PNAS 2006; 103: 19164-19169.
• 10 Krause J. SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder. Expert Rev Neurother 2008; 08: 611-625.
• 11 Krause J. et al. Influence of striatal dopamine transporter availability on the response to methylphenidate in adult patients with ADHD. Eur Arch Psychiatry Clin Neurosci 2005; 255: 428-431.
• 12 Krause KH. et al. Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: Effects of methylphenidate as measured by single photon emission computed tomography. Neurosci Lett 2000; 285: 107-110.
• 13 Tzavara ET. et al. Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine. Mol Psychiatry 2006; 11: 187-195.
• 14 Volkow ND. et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998; 155: 1325-1331.
• 15 Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 2008; 28 (Suppl. 02) S46-53.
• 16 Wilens TE, Decker MW. Neuronal nicotinic receptor agonists for the treatment of attention-deficit/ hyperactivity disorder: focus on cognition. Biochem Pharmacol 2007; 74: 1212-1223.
• 17 Yang L, Wang YF, Li J, Faraone SV. Association of norepinephrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry 2004; 43: 1154-1158.