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 (0.3mg/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.
Legendre
Onica
O
Department of Chemistry, Hunter College and the Graduate Center of the City University of New York, 695 Park Avenue, New York, NY 10065, USA.
Pecic
Stevan
S
Chaudhary
Sandeep
S
Zimmerman
Sarah M
SM
Fantegrossi
William E
WE
Harding
Wayne W
WW
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
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