PET STUDIES OF THE PHARMACOKINETICS OF D-METHAMPHETAMINE IN THE HUMAN BODY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Methamphetamine is a powerful stimulant drug, which is abused by humans. Methamphetamine abuse has become a significant public health problem not only because it is highly addictive but also because its abuse is associated with significant toxicity to the brain and other organs. The problem is exacerbated by the fact that it is readily synthesized in clandestine laboratories . Methamphetamine's principle pharmacological action is the release of dopamine and other neurotransmitters through the individual neurotransmitter transporters on presynaptic neurons. Methamphetamine-induced dopamine release is high relative to another stimulant drug, cocaine, and dopamine levels remain high over a longer period of time in laboratory animals. This results in an intense long-term stimulant effect, which is also seen in the human methamphetamine abuser. Methamphetamine induced toxicity to the brain and other organs is generally attributed to increased levels of dopamine and other catecholamines which are generally associated with oxidative damage . There are a number of biological and pharmacological factors, which may account for methamphetamine's high addictive potential and for its toxicity. One likely candidate is its pharmacokinetics in the brain and other organs. However, methamphetamine's pharmacokinetics in the human brain and in other organs are not known. Here we propose a systematic investigation of the uptake and kinetics of d-methamphetamine (the active isomer) in the brain and in peripheral organs with PET and carbon-11 labeled d-methamphetamine in a group of normal healthy non-drug abusing volunteers. We will also pair the brain study with a measure of dopamine transporter (DAT) availability using [11C]cocaine to measure DAT levels in the same individuals.