Acute effects of methcathinone and manganese in mice: A dose response study

Andres Asser1, Sulev Kõks2, Ursel Soomets3

  • 1Department of Neurology and Neurosurgery, University of Tartu, Puusepa 8, Tartu, 51014, Estonia.

Heliyon
|November 6, 2019
PubMed

Insights

This study reveals that both methcathinone (Mcat) and manganese (Mn) significantly contribute to the toxicity of an illicit drug mixture. Both components exhibit dose-dependent behavioral effects and play a role in the drug

Area of Science:

  • Neuroscience
  • Toxicology
  • Pharmacology

Background:

  • Illicit drug mixtures containing pseudoephedrine, potassium permanganate, vinegar, and water yield methcathinone (Mcat) and manganese (Mn).
  • This mixture can induce extrapyramidal syndromes resembling parkinsonism and manganism.
  • The individual toxic contributions of Mcat and Mn within the mixture are not fully understood, with Mcat's role potentially underestimated.

Purpose of the Study:

  • To investigate the dose-dependent behavioral effects of the illicit drug mixture and its primary components, Mcat and Mn, in an acute setting.
  • To determine the lethal doses (LD50) of the mixture and Mcat.
  • To elucidate the distinct roles of Mcat and Mn in the overall toxicity profile.

Main Methods:

  • C57BL/6 mice were administered varying intraperitoneal doses of the drug mixture (Mcat/Mn), pure racemic Mcat, or manganese chloride (MnCl2).
  • Locomotor activity, observable behavioral signs, and time of death were meticulously recorded for all experimental groups.
  • Dose-response relationships and lethal doses were statistically analyzed.

Main Results:

  • Low doses of Mcat (10 and 25 mg/kg) demonstrated a dose-dependent stimulant effect on motor activity.
  • High doses of Mcat induced epileptic seizures in 74% of animals and proved lethal.
  • The drug mixture also exhibited a dose-dependent stimulant effect, with higher doses being lethal. The LD50 for the mixture was 110.2 mg Mcat/kg, and for pure Mcat, it was 201.7 mg/kg.
  • Manganese (Mn) did not cause lethality up to 50 mg/kg but exhibited a strong dose-dependent inhibitory effect on behavior.

Conclusions:

  • Both manganese (Mn) and methcathinone (Mcat) play significant and distinct roles in the toxicity of the illicit drug mixture.
  • Mcat acts as a stimulant at lower doses and can induce seizures and lethality at higher doses.
  • Mn significantly inhibits behavior in a dose-dependent manner, contributing to the overall toxicological profile of the mixture.

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