3,4-methylenedioxymethamphetamine (MDMA; ecstasy) metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of...
The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoamine receptors and determined...
This PhD work consists of an in vitro and in vivo part. In the in vivo part, we investigated the role of dopamine in the acute clinical effects of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in healthy human subjects. The role of dopamine in the addictive effects of drug of abuse is well established, but whether it contributes to the acute psychotropic effects of MDMA is unclear. \nIn...
N-2-methoxybenzyl-phenethylamines (NBOMe drugs) are newly used psychoactive substances with poorly defined pharmacological properties. The aim of the present study was to characterize the receptor binding profiles of a series of NBOMe drugs compared with their 2,5-dimethoxy-phenethylamine analogs (2C drugs) and lysergic acid diethylamide (LSD) in vitro. We investigated the binding affinities of...
Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide...
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a popular recreational drug. The aim of the present study was to explore the role of dopamine in the psychotropic effects of MDMA using bupropion to inhibit the dopamine and norepinephrine transporters through which MDMA releases dopamine and norepinephrine by investigating. The pharmacodynamic and pharmacokinetic interactions between...
Background and Purpose Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro . Experimental Approach We assessed the effects of the benzofurans 5‐ APB , 5‐ APDB , 6‐ APB , 6‐ APDB , 4‐ APB , 7‐ APB , 5‐ EAPB and 5‐ MAPDB and benzodifuran 2 C ‐ B ‐ FLY on the human...
We greatly appreciate the comments offered by Drs Rolle, Takematsu and Hoffman and the opportunity to put our work into a wider perspective. We share the view that our work does not reflect the clinical situation but rather provides a proof of mechanism study, which aims to help to translate preclinical findings (Sprague et al., 2005) into the clinic. As we noted in the discussion of our work...
BACKGROUND AND PURPOSE The use of ±3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is associated with cardiovascular complications and hyperthermia. EXPERIMENTAL APPROACH We assessed the effects of the α 1 ‐ and β‐adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h...