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Pharmacology ofmethylphenidate,amphetamineenantiomers andpemoline inattention-deficithyperactivitydisorder Kennerly S. PatrickJohn S. Markowitz1997 год

Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder
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Аннотация: 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 Tmax of 1·5–2·5 h, a Cmax of 6–15 ng/ml and a T1/2 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®), 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. © 1997 John Wiley & Sons, Ltd.
Год издания: 1997
Авторы: Kennerly S. Patrick, John S. Markowitz
Издательство: Wiley
Источник: Human Psychopharmacology Clinical and Experimental
Ключевые слова: Attention Deficit Hyperactivity Disorder, Bipolar Disorder and Treatment, Neurotransmitter Receptor Influence on Behavior