Cooling down the bath salts: Carvedilol attenuation of methylone and mephedrone mediated hyperthermia. (30th November 2016)

• Record Type: Journal Article
• Authors: Zona, Luke C.; Grecco, Gregory G.; Sprague, Jon E.
• Is Part Of: Toxicology letters. Volume 263(2016)
• Page Start: 11
• Page End: 15
• Publication Date: 2016-11-30
• Subjects: MDMA 3, 4-methylenedioxymethamphetamine -- NE norepinephrine -- FFA free fatty acids -- CNS central nervous system -- DEA Drug Enforcement Administration -- DA dopamine -- 5HT serotonin -- NET norepinephrine transporter -- DAT dopamine transporter -- SERT serotonin transporter -- TAUC temperature area under the curve -- sc subcutaneous -- ip intraperitoneal; Hyperthermia -- Bath salts -- Synthetic cathinones; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.10.012
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Methylone and mephedrone induce hyperthermia. Methylone and mephedrone increase Temperature Area Under the Curve (TAUC). The α1 and β adrenergic receptor antagonist carvedilol blocks this hyperthermia. Carvedilol significantly reduced the TAUC associated with methylone or mephedrone. Abstract: The use of the synthetic cathinones ("bath salts"), methylone and mephedrone, has been associated with the development of life-threatening hyperthermia. To date, no direct pharmacological intervention to mitigate the hyperthermia induced by synthetic cathinones has been identified. Here, we investigated the effects of the non-selective α1 and β adrenergic receptor antagonist carvedilol (5 mg/kg ip) on established hyperthermia mediated by methylone and mephedrone (30 mg/kg sc) in Sprague-Dawley rats. Methylone and mephedrone induced a hyperthermic response that peaked 60 min post treatment. The administration of carvedilol 30 min after methylone or mephedrone significantly attenuated these hyperthermic responses. Analysis of the Temperature Area Under the Curve (TAUC) demonstrated carvedilol significantly reduced the TAUC associated with methylone or mephedrone alone. The present study provides the first direct pharmacological intervention for the treatment of synthetic cathinone induced hyperthermia.