The outcome of the movement disorder in methcathinone abusers: clinical,<scp>MRI</scp>and manganesemia changes, and neuropathology

Stepens, Ainārs; Groma, Valērija; Skuja, Sandra; Platkājis, Ardis; Aldiņš, P.; Eksteina, Ilze; Mārtiņsone, Inese; Bricis, Raimonds; Donaghy, Michael

doi:10.1111/ene.12185

Cited by 26 publications

(17 citation statements)

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“…Their average blood manganese levels were markedly lower and their MRI changes were less frequent and intense than those of active users. After a median period of 32.5 months, the prospective follow-up published in this issue confirms these findings [1], implying that permanent neuronal damage remained, despite resorption of manganese from the basal ganglia. This notion is enriched by the neuropathology examination of the globus pallidus biopsy from a former user, which confirmed structural damage with decompacted myelin sheaths and frequent abnormalities of mitochondria within the axons.…”

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confidence: 69%

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Methcathinone‐induced parkinsonism results from permanent brain damage: a message for the masses

Fasano

2013

Euro J of Neurology

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confidence: 69%

“…In keeping with the follow‐up study by Stepens et al . , in another recent issue of the European Journal of Neurology , Sikk et al . .…”

mentioning

confidence: 96%

Methcathinone‐induced parkinsonism results from permanent brain damage: a message for the masses

Fasano

2013

Euro J of Neurology

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“…Intravenous injections of such methcathinone preparations expose users to a high manganese load because the resultant methcathinone is not purified [75]. Although studies of methcathinone abusers have described movement disorders similar to Parkinson’s disease attributed to the manganese toxicity, the syndrome lacks typical features of this condition such as resting tremor and gait initiation failure [75]. The accumulation of manganese can lead to the development of encephalopathy and might trigger secondary pathogenic mechanisms, such as mitochondrial dysfunction and oxidative stress [76].…”

Section: Biochemical Mechanisms: Oxidative Stress and Cytotoxicitymentioning

confidence: 99%

Neurotoxicology of Synthetic Cathinone Analogs

Angoa‐Pérez

Anneken

Kuhn

2016

Current Topics in Behavioral Neurosciences

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The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in “bath salts.” Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties. Most of the literature on synthetic cathinones has focused on describing their properties as psychostimulants, their behavioral effects on locomotion, memory, and potential for abuse, whereas descriptions of their neurotoxic properties are not abundant. The biochemical gauges of neurotoxicity induced by non-keto analogs are well studied in humans and experimental animals and include their ability to induce neuroinflammation, oxidative stress, excitotoxicity, temperature alterations as well as dysregulation of neurotransmitter systems and induce changes in monoamine transporters and receptors. These neurotoxicity gauges will serve as parameters to discuss the effects of the four previously mentioned synthetic cathinones alone or in combination with either another cathinone or with some of their non-keto analogs. Bath salts are not a defined combination of drugs and may consist of one synthetic cathinone compound or combinations of more cathinones. Furthermore, this review also presents some of the mechanisms that are thought to underlie this toxicity. A better understanding of the cellular and molecular mechanisms involved in the synthetic cathinones-induced neurotoxicity should contribute to generate modern therapeutic approaches to prevent or attenuate the adverse consequences of use of these drugs in humans.

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“…Abuse of a 'homemade' version of the psychostimulant drug methcathinone (Mcat) causes a persistent and disabling extrapyramidal syndrome (Sikk et al 2011(Sikk et al , 2013Stepens et al 2014). This shares some common features with Parkinson's disease, but has distinct symptoms including early falls, dystonia, severe dysarthria, and a poor response to l-DOPA treatment (Sikk et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…This produces a solution containing high levels of both Mcat and manganese (Mn) which is then injected intravenously on multiple occasions each day (Sikk et al 2007). The neurological syndrome that appears in man is accompanied by Mn deposition in the basal ganglia and altered basal ganglia function as assessed by abnormal fluorodeoxyglucose (FDG) uptake (Sikk et al 2013;Stepens et al 2014) and decreased striatal D2 receptor binding density (Kessler et al 2003) shown by MRI and PET investigations.…”

Section: Introductionmentioning

confidence: 99%

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers

et al. 2019

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An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre-and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123 I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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The outcome of the movement disorder in methcathinone abusers: clinical,MRIand manganesemia changes, and neuropathology

Cited by 26 publications

References 29 publications

Methcathinone‐induced parkinsonism results from permanent brain damage: a message for the masses

Methcathinone‐induced parkinsonism results from permanent brain damage: a message for the masses

Neurotoxicology of Synthetic Cathinone Analogs

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers

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