S(+)-, and R(-)-3,4-methylenedioxy-N-[¹¹C]methamphetamine (MDMA, Ecstasy) were synthesized and stereochemistry was confirmed to compare pharmacokinetics of each enantiomer using positron emission tomography

Objectives 3,4-Methylenedioxymethamphetamine (MDMA), also known as“ecstasy”, is a drug with high abuse liability that represents a significant public health concern. Previous studies have indicated that the psychobiology of S(+)-MDMA is stimulant-like, whereas that of R(-)-MDMA is hallucinogen-like. Each enantiomer was labeled with carbon-11 as 3,4-methylenedioxy-N-[¹¹C]methamphetamine, and stereochemistry was confirmed by chiral HPLC, to measure pharmacokinetics with positron emission tomography.

Methods S(+)-, and R(-)-MDA•HCl were neutralized and purified as free amines. 1.7 - 2.1mg of MDA was dissolved in 170 - 210µL of DMF with a concentration of 1mg/100µL and mixed with [¹¹C]methyl iodide produced by GE TRACERlab FX C. The reaction mixture was heated at 140^oC for 10 minutes, [¹¹C]MDMA was purified by HPLC, and formulated in 15mL of physiological saline containing 10% of ethanol. The quality control was performed by HPLC coupled with a UV and a radiometric detector. The stereochemistry of each enantiomeric [¹¹C]MDMA was confirmed by Astec chirobiotic TAG^TM chiral HPLC. Data were obtained as an average of nine syntheses.

Results Decay corrected yield was 40% based on [¹¹C]methyl iodide activity, reaction time was 56 minutes from end of bombardment , specific activity at end of synthesis was 7.03GBq/µmole (0.19Ci/µmole) at end of synthesis, radiochemical purity was over 97%, and pH of a dose solution was 7. Figure 1 presents the stereochemistry and TAC curves of each enantiomeric [¹¹C]MDMA injected into non-human primates.

Conclusions S(+)-, and R(-)-[¹¹C]MDMA was synthesized with quality and reproducibility for pharmacokinetics studies in non-human primates