当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain.

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

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 drugs 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 drugs. 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.

journal_name

Life Sci

journal_title

Life sciences

authors

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

doi

10.1016/s0024-3205(99)00225-8

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

PL7-12

issue

eissn

0024-3205

issn

1879-0631

pii

S0024320599002258

journal_volume

pub_type

杂志文章

在线工具

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