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

@article{Ding1997ChiralDC,
  title={Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and l-threo-methylphenidate in the human and baboon brain},
  author={Y.‐S. Ding and Joanna S. Fowler and Nora D. Volkow and Stephen L. Dewey and G.‐J. Wang and Jean Logan and S. John Gatley and Naomi R. Pappas},
  journal={Psychopharmacology},
  year={1997},
  volume={131},
  pages={71-78}
}
Abstract  Methylphenidate (Ritalin) is the most commonly prescribed psychoactive medication for children in the US where it is used for the treatment of attention deficit hyperactivity disorder. Methylphenidate is marketed as a racemic mixture of the d-threo and l-threo enantiomers. It is believed that the d enantiomer is responsible for the therapeutic effect of methylphenidate. In this study we labeled the individual enantiomers with carbon-11 and compared their binding and pharmacokinetics… 

Methylphenidate and its Isomers

It is concluded that d-threo-methylphenidate, which is the more potent and abundant of the two isomers, is the major contributor of both efficacy and adverse effects, irrespective of the formulation or route of administration of the racemate.

Sex differences in the kinetic profiles of d- and l- methylphenidate in the brains of adult rats.

Females exhibited consistently higher brain concentrations of both d- and l- methylphenidate and a slower clearance ofethylphenidate from brain as compared to males, particularly with the active d-enantiomer.

Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?

Data from in vitro, animal, and human studies support the premise that the d-enantiomer of MPH mediates the neurophysiological actions of MPH and therefore likely mediates its clinical efficacy.

Evaluation of a new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs

An evaluation of the racemate and individual enantiomers of [11C]MRB as radioligands for PET imaging studies of NET systems in baboons both in brain and in peripheral organs suggests the enantioselectivity of MRB in vivo, consistent with previous in vitro and in vivo studies in rodents.

Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration

Results suggest that, in animal models, l‐threo‐MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and enters the brain after oral administration, but that l‐thano‐ MP may not be pharmacologically active.

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.

Kinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent.

It is suggested that the binding potential and corresponding kinetic rate constants can be reliably estimated in nonhuman primates with dynamic SPECT imaging of the dopamine transporter using a technetium-based tropane analogue.
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