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Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone).
Drug Alcohol Depend. 2013 Jan 01; 127(1-3):248-53.DA

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.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22832282

Citation

Miller, M L., et al. "Changes in Ambient Temperature Differentially Alter the Thermoregulatory, Cardiac and Locomotor Stimulant Effects of 4-methylmethcathinone (mephedrone)." Drug and Alcohol Dependence, vol. 127, no. 1-3, 2013, pp. 248-53.
Miller ML, Creehan KM, Angrish D, et al. Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug Alcohol Depend. 2013;127(1-3):248-53.
Miller, M. L., Creehan, K. M., Angrish, D., Barlow, D. J., Houseknecht, K. L., Dickerson, T. J., & Taffe, M. A. (2013). Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug and Alcohol Dependence, 127(1-3), 248-53. https://doi.org/10.1016/j.drugalcdep.2012.07.003
Miller ML, et al. 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. PubMed PMID: 22832282.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). AU - Miller,M L, AU - Creehan,K M, AU - Angrish,D, AU - Barlow,D J, AU - Houseknecht,K L, AU - Dickerson,T J, AU - Taffe,M A, Y1 - 2012/07/23/ PY - 2012/05/30/received PY - 2012/07/05/revised PY - 2012/07/09/accepted PY - 2012/7/27/entrez PY - 2012/7/27/pubmed PY - 2013/9/21/medline SP - 248 EP - 53 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 127 IS - 1-3 N2 - 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. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/22832282/Changes_in_ambient_temperature_differentially_alter_the_thermoregulatory_cardiac_and_locomotor_stimulant_effects_of_4_methylmethcathinone__mephedrone__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(12)00277-3 DB - PRIME DP - Unbound Medicine ER -