title: Influence of ketanserin on the effects of methylenedioxymethamphetamine on body temperature in the mouse.
abstract: (1) We have investigated the ability of the 5HT2 -receptor antagonist ketanserin to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and examined whether α1 -adrenoceptor antagonist actions are involved. (2) Mice were implanted with intra-abdominal temperature probes under anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg(-1) ) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry. (3) Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.24 °C at 150 min postinjection. Ketanserin (0.5 mg kg(-1) ) revealed a significant and marked early hypothermia to MDMA, an effect that is mimicked by the α1 -adrenoceptor antagonist prazosin (0.1 mg kg(-1) ). (4) Functional studies revealed antagonist actions of ketanserin at α1 -adrenoceptors in rat aorta and rat vas deferens in vitro indicative of α1 -adrenoceptor antagonist actions at the concentration used in vivo. (5) In conclusion, ketanserin (0.5 mg kg(-1) ) modulates the hyperthermic actions of MDMA in mice. Although we cannot rule out additional actions at 5HT2 -receptors, the actions of ketanserin are consistent with α1 -adrenoceptor antagonism. There is no clear evidence from this study that 5HT2-receptors mediate the hyperthermic response to MDMA.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin, Ireland.
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
authors.forename: S
authors.initials: S
authors.lastname: Bexis
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D005334:Fever / Q000139:chemically induced*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D012702:Serotonin Antagonists; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011224:Prazosin
keywords: 5HT2-receptor; MDMA; hyperthermia; hypothermia; ketanserin; α1-adrenoceptor