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: 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: 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.
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Authors | William E Fantegrossi, Christina Lynn Kiessel, P Tarn Leach, C Van Martin, Rachel Lynn Karabenick, X Chen, Y Ohizumi, Thomas Ullrich, Kenner C Rice, James H Woods |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 173
Issue 3-4
Pg. 270-7
(May 2004)
ISSN: 0033-3158 [Print] Germany |
PMID | 14740148
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Adrenergic alpha-Antagonists
- Aporphines
- Fluorobenzenes
- Piperidines
- Serotonin Agents
- Serotonin Antagonists
- volinanserin
- N-Methyl-3,4-methylenedioxyamphetamine
- nantenine
- Prazosin
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Topics |
- Adrenergic alpha-Antagonists
(pharmacology)
- Animals
- Aporphines
(administration & dosage, pharmacology)
- Behavior, Animal
(drug effects)
- Crowding
- Dose-Response Relationship, Drug
- Fever
(chemically induced, drug therapy, mortality)
- Fluorobenzenes
(pharmacology)
- Male
- Mice
- Motor Activity
(drug effects)
- N-Methyl-3,4-methylenedioxyamphetamine
(administration & dosage, antagonists & inhibitors, chemistry)
- Piperidines
(pharmacology)
- Prazosin
(pharmacology)
- Serotonin Agents
(administration & dosage, chemistry, pharmacology)
- Serotonin Antagonists
(pharmacology)
- Stereoisomerism
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