title: Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
abstract: 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 (0.3mg/kg ip) completely blocked the behavioral suppression induced upon administration of 3.0mg/kg MDMA. (+/-)-Nantenine displayed high affinity and selectivity for the alpha(1A) adrenergic receptor among several other receptors suggesting that this alpha(1) subtype may be significantly involved in the anti-MDMA effects of the enantiomers.
authors: Department of Chemistry, Hunter College and the Graduate Center of the City University of New York, 695 Park Avenue, New York, NY 10065, USA.
authors: Onica
authors: O
authors: Legendre
authors: Stevan
authors: S
authors: Pecic
authors: Sandeep
authors: S
authors: Chaudhary
authors: Sarah M
authors: SM
authors: Zimmerman
authors: William E
authors: WE
authors: Fantegrossi
authors: Wayne W
authors: WW
authors: Harding
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001067:Appetite Depressants / Q000494:pharmacology; D003500:Cyclization; D005463:Fluoroacetates; D007462:Iodobenzenes; D007650:Ketanserin / Q000494:pharmacology; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013237:Stereoisomerism; D014269:Trifluoroacetic Acid / Q000737:chemistry
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D001060:Aporphines; D001067:Appetite Depressants; D005463:Fluoroacetates; D007462:Iodobenzenes; D018340:Receptors, Adrenergic, alpha-1; C517666:phenyliodine(III) bis(trifluoroacetate); D007650:Ketanserin; D014269:Trifluoroacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C041615:nantenine