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

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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

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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.
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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.",
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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

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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