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Acute effects of methcathinone and manganese in mice: A dose response study
Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-51014 Tartu, Estonia.
Univ Western Australia, Perron Inst Neurol & Translat Sci, Perth, WA, Australia.
Univ Tartu, Dept Biochem, Ravila 19, EE-50411 Tartu, Estonia.
Univ Tartu, Dept Physiol, Ravila 19, EE-50411 Tartu, Estonia.
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2019 (English)In: HELIYON, ISSN 2405-8440, Vol. 5, no 9, article id e02475Article in journal (Refereed) Published
Abstract [en]

An intravenously injectable illicit drug made by mixing pseudoephedrine, potassium permanganate, vinegar and water, yielding methcathinone (Mcat) and manganese (Mn), induces an extrapyramidal syndrome with parkinsonism, dystonia, gait and balance disorders similar to manganism. Although the cause of the syndrome is largely attributed to Mn, the interaction of the drug's individual components is not known and the role of Mcat is possibly underestimated. Aim of the present study was to analyze dose-dependent behavioral effects of the mixture and its two main active components Mcat and Mn in an acute setting and determine the lethal doses of each substance. Three groups of C57BL/6 mice were injected intraperitoneally with (1) the drug mixture containing 10, 25, 50, 100 or 150 mg of Mcat and respectively 1.6, 3.8, 6.9, 17.1 and 22.6 mg of Mn per kilogram of body weight; (2) 10, 25, 50, 100, 150, 200 or 300 mg of racemic Mcat/kg of body weight; (3) MnCl2 10, 25 or 50 mg/kg of body weight. Locomotor activity of the animals, various signs and time of death were recorded. Lower doses (10 and 25 mg/kg) of Mcat had a clear motor activity stimulating effect and this was clearly dose-dependent. High doses of Mcat produced epileptic seizures in 74% of the animals and became lethal with the highest doses. Similarly, the mixture had a clear dose-dependent stimulating effect and the higher doses became lethal. The LD50 of the pseudoephedrine mixture was 110.2 mg of Mcat/kg and for pure Mcat 201.7 mg/kg. Mn did not prove to be lethal in doses up to 50 mg/kg, but had a strong dose dependent inhibitory effect on the animals' behavior. Our data reveal that both Mn and Mcat have a significant role in the toxicity of the mixture.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2019. Vol. 5, no 9, article id e02475
Keywords [en]
Neuroscience, Toxicology, Behavioral neuroscience, Dose-response relationship, Nervous system, Neurotoxicology, Ephedrone, Toxic parkinsonism, Manganese, Methcathinone
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-396626DOI: 10.1016/j.heliyon.2019.e02475ISI: 000488879100006OAI: oai:DiVA.org:uu-396626DiVA, id: diva2:1369838
Available from: 2019-11-13 Created: 2019-11-13 Last updated: 2019-11-13Bibliographically approved

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Eltermaa, MallUbhayasekera, KumariBergquist, Jonas
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