PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and ( )-Cocaine

• DOI: 10.2967/jnumed.107.040279
• Publication Date: 2007-09-15T01:14:59Z
• Authors: J. S. Fowler; C. Kroll; R. Ferrieri; D. Alexoff; J. Logan; S. L. Dewey; W. Schiffer; D. Schlyer; P. Carter; P. King; C. Shea; Y. Xu; L. Muench; H. Benveniste; P. Vaska; N. D. Volkow
• Keywords: Methamphetamine

The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d-methamphetamine (the more active enantiomer) l-methamphetamine less enantiomer). d-Methamphetamine is associated with intense stimulant effects higher abuse liability. objective of this study was to measure the pharmacokinetics for comparison both (-)-cocaine in baboon brain peripheral organs assess saturability pharmacologic specificity binding.d- were labeled (11)C via alkylation norprecursors (11)C-methyl iodide using literature methods. Six different baboons studied 11 PET sessions at which radiotracer injections administered 2-3 h apart determine distribution kinetics (11)C-d-methamphetamine organs. Saturability assessed pretreatment d-methamphetamine, methylphenidate, tetrabenazine. (11)C-d-Methamphetamine compared (11)C-l-methamphetamine (11)C-(-)-cocaine same animal.(11)C-d- showed high uptake widespread brain. Pharmacokinetics did not differ between cerebellum peaked earlier cleared quickly than striatum both. volume ratio substantially affected by methamphetamine, or Both enantiomers rapid, clearance heart lungs slower liver kidneys. A that later slowly. drugs similar behavior all examined except kidneys pancreas, (11)C-d-methamphetamine.Brain d-and thus cannot account d-methamphetamine. Lack blockade indicates image represents nonspecific binding, though fact transporter substrate an inhibitor may also play role. animal likely contribute its previously reported longer-lasting relative those (-)-cocaine. High kidney metabolites renal toxicity humans.