| Abstract | BACKGROUND AND PURPOSE: We have investigated the ability of alpha(1)-adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice. EXPERIMENTAL APPROACH: Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg(-1)) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored. KEY RESULTS: Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 degrees C at 140 min. Prazosin (0.1 mg kg(-1)) revealed an early significant hypothermia to MDMA of -1.94 degrees C. The alpha(1A)-adrenoceptor antagonist RS 100329 (0.1 mg kg(-1)), or the alpha(1D)-adrenoceptor antagonist BMY 7378 (0.5 mg kg(-1)) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative alpha(1B)-adrenoceptor antagonist cyclazosin (1 mg kg(-1)) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other alpha(1)-adrenoceptor subtypes cannot be excluded. CONCLUSIONS AND IMPLICATIONS: More than one subtype of alpha(1)-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both alpha(1A)- and alpha(1D)-adrenoceptors, and removal of this alpha(1)-adrenoceptor-mediated component reveals an initial hypothermia. |
| Authors | S Bexis, J R Docherty
(Affiliation: Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland.)
|
| Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 153
Issue 3
Pg. 591-7
(Feb 2008)
ISSN: 0007-1188 England |
| PMID | 18037913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Adrenergic Uptake Inhibitors
- Adrenergic alpha-Antagonists
- Piperazines
- Quinazolines
- Quinoxalines
- RS 100329
- Receptors, Adrenergic, alpha-1
- adrenergic receptor alpha(1a)
- adrenergic receptor alpha(1d)
- cyclazosin
- Prazosin
- BMY 7378
- N-Methyl-3,4-methylenedioxyamphetamine
- Thymine
|
| Topics |
- Adrenergic Uptake Inhibitors
(adverse effects, pharmacology)
- Adrenergic alpha-Antagonists
(pharmacology)
- Animals
- Body Temperature
(drug effects)
- Fever
(chemically induced)
- Male
- Mice
- N-Methyl-3,4-methylenedioxyamphetamine
(adverse effects, pharmacology)
- Piperazines
(pharmacology)
- Prazosin
(pharmacology)
- Quinazolines
(pharmacology)
- Quinoxalines
(pharmacology)
- Receptors, Adrenergic, alpha-1
(drug effects, metabolism)
- Thymine
(pharmacology)
|
