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

  title={Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention‐deficit hyperactivity disorder},
  author={Kennerly Sexton Patrick and John Seth Markowitz},
  journal={Human Psychopharmacology: Clinical and Experimental},
  • K. Patrick, J. Markowitz
  • Published 1 November 1997
  • Biology, Chemistry
  • Human Psychopharmacology: Clinical and Experimental
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… 

New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder

The newly approved resolved enantiomer product d-MPH is now available in an IR formulation, and when administered at one-half the dose to that of the racemate, is purported to produce a longer duration of clinical effect, despite essentially identical pharmacokinetics.

Stimulants and Other Non-stimulants for Attention-Deficit/Hyperactivity Disorder (ADHD)

The pharmacodynamic benefits and adverse effects of methylphenidate, amphetamines, and atomoxetine may be linked to their pharmacokinetic profiles.

Isopropylphenidate: an ester homolog of methylphenidate with sustained and selective dopaminergic activity and reduced drug interaction liability.

IPH displayed unique pharmacological characteristics including greater DAT than NET binding and cellular uptake activity, and greater resistance to hydrolysis and transesterification via carboxylesterase 1 relative to MPH.

Advances in the Pharmacotherapy of Attention‐Deficit‐Hyperactivity Disorder: Focus on Methylphenidate Formulations

The psychostimulant dl‐methylphenidate (MPH) remains the most common drug therapy in child and adolescent psychiatry for the treatment of attention‐deficit‐hyperactivity disorder (ADHD). Evidence of

The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder.

The array of AMP formulations addressed in this review offer flexibility in dosing, drug onset, and offset to assist in individualized pharmacotherapy of ADHD, and some metabolic pathways exhibit stereoselective biotransformations favoring the l-isomer substrate.

Methylphenidate transdermal system for the treatment of attention-deficit/hyperactivity disorder

MTS demonstrated significant reductions in the core symptoms of ADHD from 2 through 12 h post-application, and was approved by the US FDA in 2006 for the treatment of attention- deficit/hyperactivity disorder.

Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.

We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH

Dose‐Proportional and Stereospecific Pharmacokinetics of Methylphenidate Delivered Using an Osmotic, Controlled‐Release Oral Delivery System

Plasma concentrations of l‐methylphenidate were 40‐fold lower than those of d‐ methylphenidate, whereas plasma concentrations of d-α‐phenyl‐2‐piperidine acetic acid and l‐PPA, the major metabolite of methyl phenidate, were comparable, indicating that methylphenidates metabolism was not affected by increasing dose.


The objective of this review is to summarize the research reports that mainly have used rats as the model to investigate the action of methylphenidate.



Enantioselective pharmacokinetics and pharmacodynamics of dl‐thero‐mcthylphenidate in children with attention deficit hyperactivity disorder

The computer tests revealed a drug‐induced improvement in sustained attention that was entirely attributable to the d‐enantiomer, and there was no evidence to suggest that the effectiveness of d‐methylphenidate was in any way compromised by the presence of its antipode.

Stereoselective disposition of methylphenidate in children with attention-deficit disorder.

Six boys with attention-deficit disorder were given single doses (5 or 10 mg) of dl-threo-methylphenidate (Ritalin, Ciba-Geigy, Basel, Switzerland). Plasma samples through 8 hr were analyzed by

Evidence that dogs do not model enantioselective pharmacokinetics of dl-methylphenidate in humans.

Abstract To the Editor: Attention-deficit hyperactivity disorder (ADHD) in children is characterized by varying degrees of inattention, impulsiveness, and hyperactivity. Many children with ADHD

Psychopharmacology of attention deficit disorder: pharmacokinetic, neuroendocrine, and behavioral measures following acute and chronic treatment with methylphenidate.

The concentration of MPH in single "spot" samples obtained at two to three hours after administration of medication were significantly correlated with the percentage of improvement in the abbreviated Conners rating scale, indicating a relationship between plasma MPH concentration and clinical response.

Sustained release methylphenidate: pharmacokinetic studies in ADDH males.

Comparisons of the two sets of plasma concentration curves suggest that MPH-SR has a longer Tmax, but that it does not reach the same Cmax as an identical dose of standard MPH.

Enantioselective aspects of the disposition of dl-threo-methylphenidate after the administration of a sustained-release formulation to children with attention deficit-hyperactivity disorder.

The purpose of this present investigation was to determine whether the levels of methylphenidate were sustained for over a time period of 8 h, and to examine enantioselective aspects of the pharmacokinetics following the ingestion of the sustained-release formulation.

Distribution of methylphenidate and p-hydroxymethylphenidate in rats.

The data suggest that the central effects of MPH do not depend upon conversion to HOMPH, and that the main action of MPH is determined by itself and not by the metabolite threo-dl-p-hydroxymethylphenidate.

Pharmacology of the enantiomers of threo-methylphenidate.

Results suggest that synaptic inhibition of catecholaminergic uptake by d-threo-MPH may be involved fundamentally in behavioral and pressor effects of the racemic drug.

Pharmacokinetics and pharmacodynamics of (+)‐threo‐methylphenidate enantiomer in patients with hypersomnia

A significant correlation was found between the sleep latency as measured by the multiple sleep latency test and the plasma concentrations of (+)‐methylphenidate (r = 0.850) and the time course of theSleep latency after repeated administration was similar to that after single administration.

Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats

  • C. Braestrup
  • Biology, Psychology
    The Journal of pharmacy and pharmacology
  • 1977
The mechanisms by which the two groups ofhetamine‐like stimulants are differentiated biochemically is discussed with special attention to possible intra‐neuronal inhibition of dopamine oxidation by the ‘(+)‐amphetamine group’.