| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1375366 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
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.
Graphical abstract(S)-(+)-1 and (R)-(-)-1 block rate suppression effects induced by (±)-MDMA in rats.Figure optionsDownload full-size imageDownload as PowerPoint slide
