Titre du document / Document title

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

Auteur(s) / Author(s)

FANTEGROSSI William E. ⁽¹⁾ ; KIESSEL Christina Lynn ⁽¹⁾ ; LEACH P. Tarn ⁽¹⁾ ; VAN MARTIN C. ⁽¹⁾ ; KARABENICK Rachel Lynn ⁽¹⁾ ; CHEN X. ⁽²⁾ ; OHIZUMI Y. ⁽²⁾ ; ULLRICH Thomas ⁽³⁾ ; RICE Kenner C. ⁽³⁾ ; WOODS James H. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, Medical School, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109-0632, ETATS-UNIS
⁽²⁾ Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, 980-8578 Aoba, Aramaki, Aoba-ku, Sendai, JAPON
⁽³⁾ Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Building 8, Room B1-21, Bethesda, MD 20892, ETATS-UNIS

Résumé / 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-HT_2A 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.

Revue / Journal Title

Psychopharmacologia   ISSN 0033-3158   CODEN PSYPAG 

Source / Source

2004, vol. 173, n^o 3-4 (223 p.)  [Document : 8 p.] (32 ref.), pp. 270-277 [8 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1959) (Revue)

Mots-clés anglais / English Keywords

Vertebrata ; Mammalia ; Rodentia ; Hyperthermia ; Treatment ; Toxicity ; Mouse ; Animal ; Behavior ; Antagonist ;

Mots-clés français / French Keywords

Vertebrata ; Mammalia ; Rodentia ; Hyperthermie ; Traitement ; Toxicité ; Souris ; Animal ; Amphétamine(N-méthyl-3,4-méthylènedioxy) ; Comportement ; Antagoniste ;

Mots-clés espagnols / Spanish Keywords

Vertebrata ; Mammalia ; Rodentia ; Hipertermia ; Tratamiento ; Toxicidad ; Ratón ; Animal ; Conducta ; Antagonista ;

Mots-clés d'auteur / Author Keywords

MDMA ; Nantenine ; Toxicity ; Hyperthermia ;

Localisation / Location

INIST-CNRS, Cote INIST : 1761, 35400011029007.0050