Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone)

Drug Alcohol Depend. 2013 Jan 1;127(1-3):248-53. doi: 10.1016/j.drugalcdep.2012.07.003. Epub 2012 Jul 23.

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.

Conclusion: These results show that the cathinone analog 4-MMC exhibits in vivo thermoregulatory properties that are distinct from those produced by MDMA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Temperature / drug effects*
  • Body Temperature / physiology
  • Body Temperature Regulation / drug effects*
  • Body Temperature Regulation / physiology
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Illicit Drugs / pharmacology*
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / pharmacology
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Temperature

Substances

  • Illicit Drugs
  • Methamphetamine
  • mephedrone