Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder

✍ Scribed by Kennerly S. Patrick; John S. Markowitz

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 239 KB
• Volume: 12
• Category: Article
• ISSN: 0885-6222
• DOI: 10.1002/(sici)1099-1077(199711/12)12:6<527::aid-hup932>3.0.co;2-u

✦ Synopsis

Racemic methylphenidate remains the drug of choice for attention-de®cit 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 (À)-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 ecacy 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 1 ), 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-eects, potential hepatotoxicity relegates pemoline to a second-line status.