Methylphenidate and its Isomers

  title={Methylphenidate and its Isomers},
  author={David J. Heal and David Montague Pierce},
  journal={CNS Drugs},
Abstractdl-threo-Methylphenidate is a highly efficacious drug for treating attention-deficit hyperactivity disorder (ADHD) that is currently administered as immediate- or controlled-release and osmotically controlled-released formulations. The drug exists as two enantiomers, d-threo-methylphenidate and l-threo-methylphenidate, with the former having been developed as a medication to treat ADHD in its own right. dl-threo-Methylphenidate undergoes enantioselective metabolism in the liver, which… 

The impact of methylphenidate and its enantiomers on dopamine synthesis and metabolism in vitro

Metabolomics of Methylphenidate and Ethylphenidate: Implications in Pharmacological and Toxicological Effects

  • R. Dinis-Oliveira
  • Biology, Chemistry
    European Journal of Drug Metabolism and Pharmacokinetics
  • 2016
It is expected that knowing the metabolomics of MPH may provide further insights regarding individual contribution for MPH pharmacodynamics and toxicological effects, namely if ethanol is co-consumed.

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.

Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo and (±)-erythro diastereomers.

The identification and analytical characterization of two powdered 4F-MPH products obtained from an online vendor in 2015 suggest that the psychostimulant properties of (±)-threo-4F- MPs might be more potent in humans than MPH.

Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers

In some subjects, the pharmacologically less active l-threo -enantiomer may contribute to the total plasma methylphenidate concentrations, which might affect how the plasma concentrations of methyl phenidate are interpreted and used for clinical decision making.

Methylphenidate Transdermal System

Methylphenidate transdermal system was generally well tolerated in adolescents with ADHD and the vast majority of treatment-emergent adverse events were of mild to moderate severity in both the short-term core trial and the longer-term extension study.

The discriminative stimulus properties of methylphenidate in C57BL/6J mice

Preclinical findings provide insight into relative potency, and by extension, efficacy of dl-MPH versus d- MPH doses, as well as the threshold doses needed to produce stimulatory effects of motor activity in B6 mice.

Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review

There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD.



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.

Comparative pharmacodynamics and plasma concentrations of d-threo-methylphenidate hydrochloride after single doses of d-threo-methylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in a double-blind, placebo-controlled, crossover laboratory school study in children with attention-

The efficacy of the d-isomer was equivalent to the racemic preparation in reducing ADHD symptoms and increasing academic productivity and clinical efficacy was highly correlated with plasma concentrations of d-MPH.

D-methylphenidate and D,L-methylphenidate are not developmental toxicants in rats and rabbits.

Rats and rabbits dosed with D,L-MPH exhibited significantly greater incidence of maternal clinical observations at twice the dose of D- MPH, and both compounds were not teratogenic in rats and rabbits at higher exposure levels compared to humans.

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.

Methylphenidate Is Stereoselectively Hydrolyzed by Human Carboxylesterase CES1A1

CES1A1 is the major enzyme responsible for the first-pass, stereoselective metabolism of methylphenidate, and both enantiomers ofethylphenidate can be fit into the three-dimensional model of CES 1A1 to form productive complexes in the active site.

Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.

In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate, and a slight under-proportionality was detected in exposure with Increasing doses of D,L-MPH.

Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and l-threo-methylphenidate in the human and baboon brain

Results indicate that pharmacological specificity of MP resides entirely in the d-threo isomer and directly show that binding of the l-isomer in human brain is mostly non-specific.

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

Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.

The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration, and the peak concentration was reached within 1-2 h.

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

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