Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers
Andres Asser, Atsuko Hikima, Mari Raki, Kim Bergström, Sarah Rose, Julius Juurmaa, Villem Krispin, Mari Muldmaa, Stella Lilles, Hanna Rätsep, Peter Jenner, Sulev Kõks, Pekka T. Männistö, Pille Taba
Journal of Neural Transmission
Atsuko Hikima (Institute of Pharmaceutical Science)
Sarah Rose (Institute of Pharmaceutical Science)
Peter Jenner (Institute of Pharmaceutical Science)
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 123I-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.
Oleh Hornykiewicz, a giant in the understanding and treatment of Parkinson disease
Salvage, S., Hikima, A., Tough, I. R., Pritchard, S., Jackson, M., Jenner, P., Chaudhuri, K., Cox, H., Iravani, MM. & Coletto, E., 23 Jan 2021, In: Nature Parkinson's Journal. 7, 1, 9 p., 1.
Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson's disease
Coletto, E., Dolan, J. S., Pritchard, S., Gant, A., Hikima, A., Jackson, M. J., Benham, C. D., Ray Chaudhuri, K., Rose, S., Jenner, P. & Iravani, M. M., 25 Jun 2019, In: Nature Parkinson's Journal. 5, 10 p., 31231674.
Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia
Pritchard, S., Jackson, M. J., Hikima, A., Lione, L., Benham, C. D., Chaudhuri, K. R., Rose, S., Jenner, P. & Iravani, M. M., 17 May 2017, In: PL o S One . 12, 5, e0175797.
The selective 5-HT1A receptor agonist, NLX-112, exerts anti-dyskinetic and anti-parkinsonian-like effects in MPTP-treated marmosets
Fisher, R., Hikima, A., Morris, R., Jackson, M. J., Rose, S., Varney, M. A., Depoortere, R. & Newman-Tancredi, A., 1 May 2020, In: Neuropharmacology. 167, 107997.
The selective 5-HT1A receptor agonist, NLX-112, exerts anti-dyskinetic and antiparkinsonian-like effects in MPTP-treated marmosets
Fisher, R., Hikima, A., Morris, R., Jackson, M. J., Salvage, S., Varney, M. A., Depoortere, R. & Newman-Tancredi, A., 10 Feb 2020, In: Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2020.107997.
The Pharmacological Potential of Adenosine A 2A Receptor Antagonists for Treating Parkinson's Disease
Mori, A., Chen, J-F., Uchida, S., Durlach, C., King, S. M. & Jenner, P., 6 Apr 2022, In: Molecules (Basel, Switzerland). 27, 7, 2366.
Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease: Past, Present, and Future
Tan, Y. Y., Jenner, P. & Chen, S. D., 2022, In: Journal of Parkinson's Disease. 12, 2, p. 477-493 17 p.
Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease
EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group, Dec 2021, In: npj Parkinson's Disease. 7, 1, 48.
Dysregulation of epithelial ion transport and neurochemical changes in the colon of a parkinsonian primate
Coletto, E., Tough, I. R., Pritchard, S., Hikima, A., Jackson, M. J., Jenner, P., Ray Chaudhuri, K., Cox, H. M., Iravani, M. M. & Rose, S., Dec 2021, In: npj Parkinson's Disease. 7, 1, 9.
Rotigotine Transdermal Patch for Motor and Non-motor Parkinson's Disease: A Review of 12 Years' Clinical Experience
Raeder, V., Boura, I., Leta, V., Jenner, P., Reichmann, H., Trenkwalder, C., Klingelhoefer, L. & Chaudhuri, K. R., Feb 2021, In: CNS Drugs. 35, 2, p. 215-231 17 p.
Viruses, parkinsonism and Parkinson's disease: the past, present and future
Leta, V., Urso, D., Batzu, L., Lau, Y. H., Mathew, D., Boura, I., Raeder, V., Falup-Pecurariu, C., van Wamelen, D. & Ray Chaudhuri, K., Sep 2022, In: Journal of Neural Transmission. 129, 9, p. 1119–1132 14 p.
Tolerability of overnight rotigotine transdermal patch combined with intrajejunal levodopa infusion at 1 year: a 24-h treatment option in Parkinson's disease
Lau, Y. H., Leta, V., Rukavina, K., Parry, M., Ann Natividad, J., Metta, V., Chung-Faye, G. & Chaudhuri, K. R., Jul 2022, In: Journal of Neural Transmission. 129, 7, p. 889-894 6 p.
Emotional well-being and pain could be a greater determinant of quality of life compared to motor severity in cervical dystonia
Klingelhoefer, L., Kaiser, M., Sauerbier, A., Untucht, R., Wienecke, M., Mammadova, K., Falkenburger, B., Gregor, O., Chaudhuri, K. R. & Reichmann, H., Mar 2021, In: Journal of Neural Transmission. 128, 3, p. 305-314 10 p.
Iron and inflammation: in vivo and post-mortem studies in Parkinson's disease
Martin-Bastida, A., Tilley, B. S., Bansal, S., Gentleman, S. M., Dexter, D. T. & Ward, R. J., Jan 2021, In: Journal of Neural Transmission. 128, 1, p. 15-25 11 p.
Implications of dopaminergic medication withdrawal in Parkinson's disease
Koschel, J., Ray Chaudhuri, K., Tönges, L., Thiel, M., Raeder, V. & Jost, W. H., 2021, (Accepted/In press) In: Journal of Neural Transmission.