Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

Nora D. Volkow, Gene Jack Wang, Joanna S. Fowler, Marian Fischman, Richard Foltin, Naji N. Abumrad, Samuel J. Gatley, Jean Logan, Cristopher Wong, Andrew Gifford, Yu Shin Ding, Robert Hitzemann, Naomi Pappas

Research output: Contribution to journalArticle

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Abstract

The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drags could account for the differences in their abuse liability we compared the levels of DAT occupancies that we had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [11C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drags. Methylphenidate and cocaine produced comparable dose-dependent blockade of DAT with an estimated ED50 (dose required to block 50% of the DAT) for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine. The similar in vivo potencies at the DAT for methylphenidate than for cocaine are in agreement with their reported relative in vitro affinities (Ki 390 nM and 640 nM respectively), which is likely to reflect the similar degree of uptake (8-10% of the injected dose) and regional distribution of these two drugs in the human brain. Thus, differences in the in vivo potency of these two drugs at the DAT cannot be responsible for the differences in their rate of abuse in humans. Other variables i.e. longer duration of methylphenidate's side effects may counterbalance its reinforcing effects.

Original languageEnglish (US)
JournalLife Sciences
Volume65
Issue number1
DOIs
StatePublished - May 28 1999
Externally publishedYes

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Dopamine Plasma Membrane Transport Proteins
Methylphenidate
Cocaine
Brain
Drag
Pharmaceutical Preparations
Positron emission tomography
Blood pressure
Positron-Emission Tomography
Cerebellum

Keywords

  • Addiction
  • ADHD
  • Imaging
  • PET
  • Reinforcement

ASJC Scopus subject areas

  • Pharmacology

Cite this

Volkow, N. D., Wang, G. J., Fowler, J. S., Fischman, M., Foltin, R., Abumrad, N. N., ... Pappas, N. (1999). Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sciences, 65(1). https://doi.org/10.1016/S0024-3205(99)00225-8

Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. / Volkow, Nora D.; Wang, Gene Jack; Fowler, Joanna S.; Fischman, Marian; Foltin, Richard; Abumrad, Naji N.; Gatley, Samuel J.; Logan, Jean; Wong, Cristopher; Gifford, Andrew; Ding, Yu Shin; Hitzemann, Robert; Pappas, Naomi.

In: Life Sciences, Vol. 65, No. 1, 28.05.1999.

Research output: Contribution to journalArticle

Volkow, ND, Wang, GJ, Fowler, JS, Fischman, M, Foltin, R, Abumrad, NN, Gatley, SJ, Logan, J, Wong, C, Gifford, A, Ding, YS, Hitzemann, R & Pappas, N 1999, 'Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain', Life Sciences, vol. 65, no. 1. https://doi.org/10.1016/S0024-3205(99)00225-8
Volkow, Nora D. ; Wang, Gene Jack ; Fowler, Joanna S. ; Fischman, Marian ; Foltin, Richard ; Abumrad, Naji N. ; Gatley, Samuel J. ; Logan, Jean ; Wong, Cristopher ; Gifford, Andrew ; Ding, Yu Shin ; Hitzemann, Robert ; Pappas, Naomi. / Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. In: Life Sciences. 1999 ; Vol. 65, No. 1.
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abstract = "The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drags could account for the differences in their abuse liability we compared the levels of DAT occupancies that we had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [11C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drags. Methylphenidate and cocaine produced comparable dose-dependent blockade of DAT with an estimated ED50 (dose required to block 50{\%} of the DAT) for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine. The similar in vivo potencies at the DAT for methylphenidate than for cocaine are in agreement with their reported relative in vitro affinities (Ki 390 nM and 640 nM respectively), which is likely to reflect the similar degree of uptake (8-10{\%} of the injected dose) and regional distribution of these two drugs in the human brain. Thus, differences in the in vivo potency of these two drugs at the DAT cannot be responsible for the differences in their rate of abuse in humans. Other variables i.e. longer duration of methylphenidate's side effects may counterbalance its reinforcing effects.",
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