Psychopharmacology

, Volume 173, Issue 3, pp 270–277

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

Authors

    • Department of Pharmacology, Medical SchoolUniversity of Michigan
  • Christina Lynn Kiessel
    • Department of Pharmacology, Medical SchoolUniversity of Michigan
  • P. Tarn Leach
    • Department of Pharmacology, Medical SchoolUniversity of Michigan
  • C. Van Martin
    • Department of Pharmacology, Medical SchoolUniversity of Michigan
  • Rachel Lynn Karabenick
    • Department of Pharmacology, Medical SchoolUniversity of Michigan
  • X. Chen
    • Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical SciencesTohoku University
  • Y. Ohizumi
    • Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical SciencesTohoku University
  • Thomas Ullrich
    • Laboratory of Medicinal Chemistry, NIDDKNational Institutes of Health
  • Kenner C. Rice
    • Laboratory of Medicinal Chemistry, NIDDKNational Institutes of Health
  • James H. Woods
    • Department of Pharmacology, Medical SchoolUniversity of Michigan
Original Investigation

DOI: 10.1007/s00213-003-1741-2

Cite this article as:
Fantegrossi, W.E., Kiessel, C.L., Leach, P.T. et al. Psychopharmacology (2004) 173: 270. doi:10.1007/s00213-003-1741-2

Abstract

Rationale

No 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.

Objectives

To 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 antagonist M100907.

Methods

Pretreatments of either 10 mg/kg nantenine or 1 mg/kg prazosin were administered 15 min before 32 mg/kg MDMA; core temperature and locomotor stimulation were then monitored via radiotelemetry for at least 3 h. In further hyperthermia studies, 32 mg/kg MDMA was administered first and temperature was allowed to rise for 30 min; 10 mg/kg nantenine, 1 mg/kg prazosin, or 1 mg/kg M100907 was then administered in an attempt to reverse MDMA-induced hyperthermia. In lethality assays, percent lethality was quantified 2 h after MDMA injection in two distinct housing conditions, one or 12 mice per cage, with or without 15 min pretreatments of 10 mg/kg nantenine or 1 mg/kg prazosin. Drug elicited head twitches were quantified for 10 min following administration of either MDMA enantiomer, with and without pretreatments of 1 mg/kg nantenine, 0.1 mg/kg prazosin, or 0.001 mg/kg M100907.

Results

Nantenine blocked and rapidly reversed MDMA-induced hyperthermia, attenuated lethality in both housing conditions, and reduced MDMA-induced locomotor stimulation and head twitches in mice. Prazosin blocked, but did not reverse, MDMA-induced hyperthermia, attenuated lethality (more effectively in singly-housed animals), and reduced MDMA-induced locomotor stimulation and head twitches. M100907 did not reverse MDMA-induced hyperthermia, but effectively blocked drug-elicited head twitches.

Conclusions

Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints.

Keywords

MDMANantenineToxicityHyperthermia

Copyright information

© Springer-Verlag 2004