Synthetic studies and pharmacological evaluations on the MDMA (‘Ecstasy’) antagonist nantenine

The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (±)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the importance of the chiral center of nantenine with regards to its capacity to antagonize the effects of MDMA in vivo, (R)- and (S)-nantenine were prepared and evaluated in a food-reinforced operant task in rats. Pretreatment with either nantenine enantiomer (0.3 mg/kg ip) completely blocked the behavioral suppression induced upon administration of 3.0 mg/kg MDMA. (±)-Nantenine displayed high affinity and selectivity for the α1A adrenergic receptor among several other receptors suggesting that this α1 subtype may be significantly involved in the anti-MDMA effects of the enantiomers.

(S)-(+)-1 and (R)-(-)-1 block rate suppression effects induced by (±)-MDMA in rats.Figure optionsDownload as PowerPoint slide