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

Andres Asser, Sulev Kõks, Ursel Soomets, Anton Terasmaa, Martin Sauk, Mall Eltermaa, Piret Piip, Kumari Ubhayasekera, Jonas Bergquist, Pille Taba

    Research output: Contribution to journalArticle

    Abstract

    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.

    Original languageEnglish
    Article numbere02475
    JournalHeliyon
    Volume5
    Issue number9
    DOIs
    Publication statusPublished - 1 Sep 2019

    Fingerprint

    Manganese
    Pseudoephedrine
    Body Weight
    monomethylpropion
    Potassium Permanganate
    Animal Behavior
    Dystonia
    Lethal Dose 50
    Parkinsonian Disorders
    Street Drugs
    Locomotion
    Drug Interactions
    Gait
    Inbred C57BL Mouse
    Acetic Acid
    Epilepsy
    Motor Activity
    Injections
    Water

    Cite this

    Asser, A., Kõks, S., Soomets, U., Terasmaa, A., Sauk, M., Eltermaa, M., ... Taba, P. (2019). Acute effects of methcathinone and manganese in mice: A dose response study. Heliyon, 5(9), [e02475]. https://doi.org/10.1016/j.heliyon.2019.e02475
    Asser, Andres ; Kõks, Sulev ; Soomets, Ursel ; Terasmaa, Anton ; Sauk, Martin ; Eltermaa, Mall ; Piip, Piret ; Ubhayasekera, Kumari ; Bergquist, Jonas ; Taba, Pille. / Acute effects of methcathinone and manganese in mice : A dose response study. In: Heliyon. 2019 ; Vol. 5, No. 9.
    @article{6f2cd84c2c524931af1260c780314b1e,
    title = "Acute effects of methcathinone and manganese in mice: A dose response study",
    abstract = "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.",
    keywords = "Behavioral neuroscience, Dose-response relationship, Ephedrone, Manganese, Methcathinone, Nervous system, Neuroscience, Neurotoxicology, Toxic parkinsonism, Toxicology",
    author = "Andres Asser and Sulev K{\~o}ks and Ursel Soomets and Anton Terasmaa and Martin Sauk and Mall Eltermaa and Piret Piip and Kumari Ubhayasekera and Jonas Bergquist and Pille Taba",
    year = "2019",
    month = "9",
    day = "1",
    doi = "10.1016/j.heliyon.2019.e02475",
    language = "English",
    volume = "5",
    journal = "Heliyon",
    issn = "2405-8440",
    publisher = "Elsevier",
    number = "9",

    }

    Asser, A, Kõks, S, Soomets, U, Terasmaa, A, Sauk, M, Eltermaa, M, Piip, P, Ubhayasekera, K, Bergquist, J & Taba, P 2019, 'Acute effects of methcathinone and manganese in mice: A dose response study' Heliyon, vol. 5, no. 9, e02475. https://doi.org/10.1016/j.heliyon.2019.e02475

    Acute effects of methcathinone and manganese in mice : A dose response study. / Asser, Andres; Kõks, Sulev; Soomets, Ursel; Terasmaa, Anton; Sauk, Martin; Eltermaa, Mall; Piip, Piret; Ubhayasekera, Kumari; Bergquist, Jonas; Taba, Pille.

    In: Heliyon, Vol. 5, No. 9, e02475, 01.09.2019.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Acute effects of methcathinone and manganese in mice

    T2 - A dose response study

    AU - Asser, Andres

    AU - Kõks, Sulev

    AU - Soomets, Ursel

    AU - Terasmaa, Anton

    AU - Sauk, Martin

    AU - Eltermaa, Mall

    AU - Piip, Piret

    AU - Ubhayasekera, Kumari

    AU - Bergquist, Jonas

    AU - Taba, Pille

    PY - 2019/9/1

    Y1 - 2019/9/1

    N2 - 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.

    AB - 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.

    KW - Behavioral neuroscience

    KW - Dose-response relationship

    KW - Ephedrone

    KW - Manganese

    KW - Methcathinone

    KW - Nervous system

    KW - Neuroscience

    KW - Neurotoxicology

    KW - Toxic parkinsonism

    KW - Toxicology

    UR - http://www.scopus.com/inward/record.url?scp=85072286477&partnerID=8YFLogxK

    U2 - 10.1016/j.heliyon.2019.e02475

    DO - 10.1016/j.heliyon.2019.e02475

    M3 - Article

    VL - 5

    JO - Heliyon

    JF - Heliyon

    SN - 2405-8440

    IS - 9

    M1 - e02475

    ER -

    Asser A, Kõks S, Soomets U, Terasmaa A, Sauk M, Eltermaa M et al. Acute effects of methcathinone and manganese in mice: A dose response study. Heliyon. 2019 Sep 1;5(9). e02475. https://doi.org/10.1016/j.heliyon.2019.e02475