La Influència de l'estereroquímica en el metabolisme de la 3,4-metilendioximetamfetamina (MDMA, èxtasi)

Resumen

MDMA is the head of entactogenic compounds. Its consumption causes acute toxicity and mid/long term serotonergic neurodegeneration. It is postulated that a metabolic bioactivation may be responsible for development of neurotoxicity. MDMA has a stereogenic center. It is consumed as a racemate, but its enantiomers have different pharmacological profiles. Also, MDMA presents an enantioselective and self-inhibited metabolic disposition (CYP2D6). The present thesis shows data about enantioselective metabolic disposition of MDMA in recreative consumers that participated in a clinical trial (dose: 100 mg). It was synthesised reference material and it was developed methodology for both enantioselective and diastereoselective analysis MDMA and its main metabolites. It was studied the enantioselectivity in the metabolism after 48h post-administration. (R)-MDMA/(S)-MDMA ratios were >1 and increasing over time. Major metabolites ratios were practically constant and close to 1, possibly because of the metabolic inhibition of CYP2D6 and the role of other non-enantioselective enzymes.