Role of α1- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse
| Autor: | Sotiria Bexis, James R. Docherty |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Hyperthermia medicine.medical_specialty Fever Hydrochloride Ratón N-Methyl-3 4-methylenedioxyamphetamine In Vitro Techniques Pharmacology Body Temperature Propanolamines Mice chemistry.chemical_compound Receptors Adrenergic alpha-1 Internal medicine medicine Prazosin Animals Antagonist MDMA Hypothermia medicine.disease Research Papers Rats Mice Inbred C57BL Endocrinology chemistry Receptors Adrenergic beta-3 Adrenergic beta-3 Receptor Antagonists medicine.symptom Antagonism Protein Binding medicine.drug |
| Zdroj: | British Journal of Pharmacology. 158:259-266 |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | Background and purpose: We have investigated the ability of the β3-adrenoceptor antagonist 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4,-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride (SR59230A) to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and whether α1-adrenoceptor antagonist actions are involved. Experimental approach: Mice were implanted with temperature probes under anaesthesia, and allowed 2 week recovery. MDMA (20 mg·kg−1) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry. Key results: Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.8°C at 130 min post injection. A low concentration of SR59230A (0.5 mg·kg−1) produced a small but significant attenuation of the slowly developing hyperthermia to MDMA. A high concentration of SR59230A (5 mg·kg−1) revealed a significant and marked early hypothermic reaction to MDMA, an effect that was mimicked by the α1-adrenoceptor antagonist prazosin. Functional and ligand binding studies revealed actions of SR59230A at α1-adrenoceptors. Conclusions and implications: 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4,-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride in high concentrations modulates the hyperthermic actions of MDMA in mice in two ways: by blocking an early α1-adrenoceptor-mediated component to reveal a hypothermia, and by a small attenuation of the later hyperthermic component which may possibly be β3-adrenoceptor-mediated (this seen with the low concentration of SR59230A). Hence, the major actions of SR59230A in modulating the actions of MDMA on temperature involve α1-adrenoceptor antagonism. |
| Databáze: | OpenAIRE |
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