MDMA pharmacology in humans and serotonergic effects
Year: 2013
Type: dissertation
Abstract: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most abused recreational drugs in the world. It has been extensively reported that this drug inhibits its own metabolism by inhibiting a polymorphic liver enzyme, CYP2D6, which is responsible for the clearance of one quarter of drugs used in therapeutics. This phenomenon has important clinical implications, since MDMA users display a higher prevalence of psychopathology, particularly of mood disorders, compared to control population. Importantly, these psychiatric diseases are treated with drugs most of them substrate of this enzyme. In addition, it is not elucidated how MDMA is still metabolically cleared even after repeated drug doses. Therefore, the first part of this thesis was focused on studying the metabolic autoinhibition by MDMA assessing several liver enzyme activities in men and women. Although MDMA pharmacology is well established, is it still not clear which is the mechanism of action of the drug. MDMA interacts with the serotonergic system at several levels, but nowadays is technically difficult to study the serotonergic function in living human brain. Imaging methods are limited by a number of factors. Thus, it would be advantageous to have a reliable peripheral index of the serotonergic activity in the blood. The second part of this thesis presents the development of several approaches aimed to assess whether the serotonin transporter in platelets can be used as a peripheral biomarker for central serotonergic activity, and determine if it plays any role in drug mechanism of action.
Authors: Yubero Lahoz, Samanta
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2242039006