title: Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone).
abstract: BACKGROUND
  The substituted cathinone compound known as mephedrone (4-methylmethcathinone; 4-MMC) has become popular with recreational users of psychomotor-stimulant compounds. Only recently have the first preclinical studies provided information about this drug in the scientific literature; nevertheless, media reports have led to drug control actions in the UK and across several US states. Rodent studies indicate that 4-MMC exhibits neuropharmacological similarity to 3,4-methylenedioxymethamphetamine (MDMA) and prompt investigation of the thermoregulatory, cardiac and locomotor effects of 4-MMC. This study focuses on the role of ambient temperature, which has been shown to shift the effects of MDMA from hyperthermic to hypothermic.
  
  
  METHODS
  Male Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1.0-5.6 mg/kg) using an implantable radiotelemetry system under conditions of low (20 °C) and high (30 °C) ambient temperature.
  
  
  RESULTS
  A pharmacokinetic study found a T(max) of 0.25 h and a C(max) of 1206 ng/ml after 5.6 mg/kg 4-MMC. A dose-dependent reduction of body temperature was produced by 4-MMC at 20 °C but there was no temperature change at 30 °C. Increased locomotor activity was observed after 4-MMC administration under both ambient temperatures, however, significantly more activity was observed at 30 °C. Heart rate was slowed by 1.0 and 5.6 mg/kg 4-MMC at 20°C, and was slower in the 30 °C vs. 20 °C condition across all treatments.
  
  
  CONCLUSIONS
  These results show that the cathinone analog 4-MMC exhibits in vivo thermoregulatory properties that are distinct from those produced by MDMA.
authors: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors: M L
authors: ML
authors: Miller
authors: K M
authors: KM
authors: Creehan
authors: D
authors: D
authors: Angrish
authors: D J
authors: DJ
authors: Barlow
authors: K L
authors: KL
authors: Houseknecht
authors: T J
authors: TJ
authors: Dickerson
authors: M A
authors: MA
authors: Taffe
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D013287:Illicit Drugs; D008694:Methamphetamine; C548233:mephedrone