Neurosci Biobehav Rev. 2003 Nov;27(7):615-21. Related Articles, Links
Serum and brain concentrations of methylphenidate: implications for use and
abuse.
Swanson JM, Volkow ND.
UCI: Child Development Center, University of California, 19722 MacArthur
Boulevard, Irvine, CA 92612-4480, USA. [email hidden]
When used to treat children with Attention Deficit Hyperactivity Disorder,
methylphenidate (MPH) acts primarily by blocking the dopamine (DA)
transporter (DAT) and increasing extracellular DA in the striatum. This is
strikingly similar to the mechanism of action of cocaine, a primary
stimulant drug of abuse. When administered intravenously, MPH like cocaine
has reinforcing effects (euphoria) at doses that exceed a DAT blockade
threshold of 60%. When administered orally at clinical doses, the
pharmacological effects of MPH also exceed this threshold, but reinforcing
effects rarely occur. Here we discuss the pharmacokinetic properties of MPH
in serum (and in brain) that differ for oral and intravenous routes of
administration and the importance of acute tolerance in determining
pharmacodynamic effects in clinical use and illegal abuse. We suggest that
intravenous administration of MPH mimics the rapid phasic cell firing of DA
neurons, which may be a critical factor associated with reinforcing effects
and abuse, while oral administration of MPH mimics the tonic DA cell firing,
which may be a critical factor associated with clinical effects.
PMID: 14624806 [PubMed - in process]