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Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine.
Pharmacol Biochem Behav. 2020 04; 191:172871.PB

Abstract

RATIONALE

Synthetic psychoactive cathinones (SPCs) are drugs with psychostimulant and entactogenic properties like methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). Despite clinical reports of human overdose, it remains to be determined if SPCs have greater propensity for adverse effects than MA or MDMA.

OBJECTIVES

To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA.

METHODS

Male and female C57Bl/6J mice received single injections of one of 6 doses of a test drug (0-160 mg/kg IP). Temperature and behavioral observations were taken every 20 min for 2 h followed by euthanasia of surviving mice. Organs were weighed and evaluated for histopathological changes.

RESULTS

LD50 values for MA and MDMA, 84.5 and 100.9 mg/kg respectively, were similar to previous observations. The LD50 for MMC was 118.8 mg/kg, but limited lethality was observed for other SPCs (CAT, MCAT, MDPV), so LD50 values could not be calculated. For all drugs, death was associated with seizure, when it was observed. Rather than hyperthermia, dose-dependent hypothermia was observed for MMC, MDPV, CAT, and MCAT. Contrary to initial expectations, none of the SPCs studied here had LD50 values lower than MA or MDMA.

CONCLUSIONS

These data indicate that, under the conditions studied here: (1) SPCs exhibit less lethality than MA and MDMA; (2) SPCs impair thermoregulation; (3) effects of SPCs on temperature appear to be independent of effects on lethality.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America.Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America.Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America.Department of Pharmacology and Experimental Therapeutics, University of Toledo College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States of America. Electronic address: frank.hall@utoledo.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32061662

Citation

Muskiewicz, Dawn E., et al. "Synthetic Psychoactive Cathinones: Hypothermia and Reduced Lethality Compared to Methamphetamine and Methylenedioxymethamphetamine." Pharmacology, Biochemistry, and Behavior, vol. 191, 2020, p. 172871.
Muskiewicz DE, Resendiz-Gutierrez F, Issa O, et al. Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine. Pharmacol Biochem Behav. 2020;191:172871.
Muskiewicz, D. E., Resendiz-Gutierrez, F., Issa, O., & Hall, F. S. (2020). Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine. Pharmacology, Biochemistry, and Behavior, 191, 172871. https://doi.org/10.1016/j.pbb.2020.172871
Muskiewicz DE, et al. Synthetic Psychoactive Cathinones: Hypothermia and Reduced Lethality Compared to Methamphetamine and Methylenedioxymethamphetamine. Pharmacol Biochem Behav. 2020;191:172871. PubMed PMID: 32061662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthetic psychoactive cathinones: hypothermia and reduced lethality compared to methamphetamine and methylenedioxymethamphetamine. AU - Muskiewicz,Dawn E, AU - Resendiz-Gutierrez,Federico, AU - Issa,Omar, AU - Hall,F Scott, Y1 - 2020/02/12/ PY - 2019/08/30/received PY - 2019/12/16/revised PY - 2020/02/11/accepted PY - 2021/04/01/pmc-release PY - 2020/2/18/pubmed PY - 2021/1/8/medline PY - 2020/2/17/entrez KW - Cathinone KW - Lethality KW - Mephedrone KW - Methamphetamine KW - Methcathinone KW - Methylenedioxymethamphetamine KW - Methylenedioxypyrovalerone KW - Synthetic psychoactive cathinones KW - Temperature regulation SP - 172871 EP - 172871 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 191 N2 - RATIONALE: Synthetic psychoactive cathinones (SPCs) are drugs with psychostimulant and entactogenic properties like methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). Despite clinical reports of human overdose, it remains to be determined if SPCs have greater propensity for adverse effects than MA or MDMA. OBJECTIVES: To determine whether the SPCs cathinone (CAT), methcathinone (MCAT), mephedrone (MMC), and methylenedioxypyrovalerone (MDPV) have lower LD50 values than MA or MDMA. METHODS: Male and female C57Bl/6J mice received single injections of one of 6 doses of a test drug (0-160 mg/kg IP). Temperature and behavioral observations were taken every 20 min for 2 h followed by euthanasia of surviving mice. Organs were weighed and evaluated for histopathological changes. RESULTS: LD50 values for MA and MDMA, 84.5 and 100.9 mg/kg respectively, were similar to previous observations. The LD50 for MMC was 118.8 mg/kg, but limited lethality was observed for other SPCs (CAT, MCAT, MDPV), so LD50 values could not be calculated. For all drugs, death was associated with seizure, when it was observed. Rather than hyperthermia, dose-dependent hypothermia was observed for MMC, MDPV, CAT, and MCAT. Contrary to initial expectations, none of the SPCs studied here had LD50 values lower than MA or MDMA. CONCLUSIONS: These data indicate that, under the conditions studied here: (1) SPCs exhibit less lethality than MA and MDMA; (2) SPCs impair thermoregulation; (3) effects of SPCs on temperature appear to be independent of effects on lethality. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/32061662/Synthetic_psychoactive_cathinones:_hypothermia_and_reduced_lethality_compared_to_methamphetamine_and_methylenedioxymethamphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(19)30419-8 DB - PRIME DP - Unbound Medicine ER -