MDMA (3,4-methylenedioxy methamphetamine) is a psychoactive drug which is thought to act via stimulation of secretion as well as inhibition of re-uptake of large amounts of serotonin, noradrenaline and dopamine in the brain. MDMA also acts directly on a number of receptors, including 5-HT2A receptors. There is considerable evidence that 5-HT2A antagonists can modulate behavioral and physiological effects of MDMA in animals. Nantenine an aporphine alkaloid ex Nandina domestica has been reported to block and reverse a range of behavioral and physiological effects of MDMA in mice. It is known that nantenine has moderate 5-HT2A antagonist activity. However, very little structure-activity relationship (SAR) studies have been performed on nantenine in relation to its antagonist activity at the 5-HT2A receptor. We have prepared a library of novel analogs to investigate the structural requirements for nantenine's 5-HT2A activity. Our studies demonstrate that N-methyl group and structural rigidity of the aporphine nucleus are important for activity, but that appropriate substitutions on the aromatic aporphine core can improve 5-HT2A antagonist activity. Further details of our SAR study as well as results of molecular docking experiments will be presented.

Synthesis, biological evaluation and molecular modeling of nantenine as a 5-HT<sub>2A</sub> receptor antagonist

239th National Meeting (2010)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Synthesis, biological evaluation and molecular modeling of nantenine as a 5-HT2A receptor antagonist

Synthesis, biological evaluation and molecular modeling of nantenine as a 5-HT_2A receptor antagonist