Clinical psychopharmacology of AD/HD: implications for animal models

A working knowledge of the clinical psychopharmacology of the psychostimulants in AD/HD is essential to the development of valid animal models of the disorder. The clinical pharmacokinetics and pharmacodynamics of D-amphetamine (D-AMP) and methylphenidate (MPH) have been well-studied. The plasma half-life of these compounds in children is approximately 5 h, with an onset of therapeutic action within a half-hour, and peak action at 1-3 h. The effective dose range for D-AMP in children is 0.2-0.5 mg/kg, and for MPH 0.3-1.0 mg/kg. In humans, psychostimulants bring about reductions in activity level and impulsivity, and improvement in attention span. Enhancement of executive processes mediated in the pre-frontal cortex in humans (especially tolerance for delay) is believed to mediate these therapeutic effects. There are no long-term remedial effects of the drug on behavior-i.e. symptoms return when the drugs are withdrawn. When used in the therapeutic dose range, there is no evidence of the development of significant tolerance or sensitization. These and other clinical findings to be discussed must guide and constrain the development of animal models of stimulant drug effects in AD/HD.