Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice

  title={Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice},
  author={W. Fantegrossi and Christina L. Kiessel and Prescott T. Leach and C Martin and Rachel Lynn Karabenick and X C Chen and Yasushi Ohizumi and Thomas Ullrich and Kenner C. Rice and James H. Woods},
RationaleNo selective antagonists for the effects of MDMA have yet been identified. The structurally-similar, naturally-occurring plant alkaloid nantenine (9,10-methylenedioxy-1,2 dimethoxyaporphine) may represent such a compound.ObjectivesTo investigate the capacity of nantenine to block and/or reverse MDMA-induced hyperthermia, lethality, locomotor stimulation, and head twitches in mice, and to compare these actions with those of the selective α1 antagonist prazosin and the selective 5-HT2A… 

Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and its enantiomers in the mouse

The effects of S(+)-MDMA on core temperature and head twitch behavior are consistent with a mechanism involving 5-HT release, whereas the effects of R(−)- MDMA on head twitch Behavior are inconsistent with a direct agonist mechanism of action.

MDMA-like behavioral effects of N-substituted piperazines in the mouse

Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats

The behavioral pharmacology of hallucinogens.

Preclinical characterization of toluene as a non-classical hallucinogen drug in rats: participation of 5-HT, dopamine and glutamate systems

Toluene stimulates 5HT2A and 5 HT2C receptors, and increases 5-HT and DA levels, similar to those produced by ketamine and involve activation of a complex neurotransmitter network that includes NMDA receptor antagonism.



Vascular actions of MDMA involve α1 and α2‐adrenoceptors in the anaesthetized rat

It is concluded that the initial pressor response to MDMA (5 mg kg−1) in anaesthetized rats involves α2‐ and possibly α1‐adrenoceptors and 5‐HT2 receptors, the pressor component at 1 min is largely α1 • adrenoceptor mediated, and the sustained depressor response involves α3‐and‐possibly α1•adrenOceptors.

Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine ("ecstasy") and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice

The MDMA isomers have heterogeneous effects that can be demonstrated across a wide range of endpoints and were differentially attenuated by the various serotonergic pretreatments and manipulation of the ambient temperature across housing conditions.

Hypothalamic-Pituitary-Thyroid Axis and Sympathetic Nervous System Involvement in Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy)

The mechanisms of thermogenesis induced by MDMA seem to result from an interaction between the hypothalamic-pituitary-thyroid axis and the sympathetic nervous system, wherein mechanisms leading to core and skeletal muscle hyperthermia after MDMA exposure seem to be differentially regulated by α1- and β3-adrenergic receptors.

Intravenous administration of ecstasy (3,4-methylendioxymethamphetamine) enhances cortical and striatal acetylcholine release in vivo.

Pharmacological effects of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, in several rat isolated tissues.

The results indicate that the pharmacological effects of (+)-nantenine observed at concentrations lower than 1 microM can be attributed to alpha 1 -adrenergic and 5-HT 2A receptor blocking properties whereas at higher concentrations (>1 microM) the pharmacologically activity of this natural compound may be also due to a decrease of Ca2+ influx through transmembrane calcium channels (calcium antagonist activity).