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Title: Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder
Author: Patrick, KS; Markowitz, JS
Abstract: Racemic methylphenidate remains the drug of choice for attention-deficit hyperactivity disorder (ADHD). Methylphenidate appears to produce psychostimulation by inhibiting the presynaptic uptake of impulse-released dopamine. The absolute bioavailability of methylphenidate in humans is quite low and variable: mean 23 per cent for the therapeutic (+)-isomer and 5 per cent for the (-)-isomer. The primary site of presystemic metabolism may be the gut and/or intestinal wall. Brain concentrations of methylphenidate average eight times that of blood. A T-max of 1.5-2.5 h, a C-max of 6-15 ng/ml and a T-1/2 of 2-3.5 h are typical. The area under the plasma concentration-time curves for immediate-release versus sustained-release formulations are nearly identical, but the relative efficacy is unresolved. Dextroamphetamine has generally been found to compare favourably with methylphenidate in ADHD; it acts through release of newly synthesized dopamine. Levoamphetamine is present as a minor component in a combination product (Adderall(R)), but the rationale for inclusion of the levo isomer remains unclear. Pemoline appears to both release and block the uptake of dopamine. Though rarely exhibiting sympathomimetic side-effects, potential hepatotoxicity relegates pemoline to a second-line status. (C) 1997 John Wiley & Sons, Ltd.
Source: HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
Publication Year: 1997
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