The present study was conducted with the objective of further developing the cholinergic hypothesis and not using the prevalent amyloid beta plaque hypothesis or the tau protein hypothesis on dementia. The experiment was conducted on mice using anticholinergic drugs scopolamine and biperiden to investigate the root cause of dementia. First, we measured the mice serum for liquid chromatography-tandem mass spectrometry (LC-MS/MS) after administration of scopolamine and biperiden and found an accumulation of anticholinergic drugs metabolites in the body. The Y-maze test and measurement of LC-MS/MS in the cranial skeletal muscle cells showed that the Scopolamine metabolites have a significant effect on the cranial skeletal muscles, leading to the conclusion that Methocarbamol is an effective treatment for dementia.
References
[1]
Sugimoto, H., Yamanishi, Y., Ogura, H., Iimura, Y. and Yamatsu, K. (1999) Discovery and Development of Donepezil Hydrochloride for the Treatment of Alzheimer’s Disease. Journal of the Pharmaceutical Society of Japan, 119, 101-113.
https://doi.org/10.1248/yakushi1947.119.2_101
[2]
Sugimoto, H. (2018) Make a Miracle of Drug Discovery. Monthly Isiyakusingaku, Genbunsha, 2-7. http://www.isiyaku.com/
[3]
Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y.K., Arthur, A., Myint, P.K., Grossi, C.M., Mattishent, K., Bennett, K., Campbell, N.L., Boustani, M., Robinson, L., Brayne, C., Matthews, F.E. and Savva, G.M. (2018) Anticholinergic Drugs and Risk of Dementia: Case-Control Study. British Medical Journal, 361, k1315.
https://doi.org/10.1136/bmj.k1315
[4]
Coupland, C.A.C., Hill, T., Dening, T., Morriss, R., Moore, M. and Hippisley-Cox, J. (2019) Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Internal Medicine.
[5]
Prohovnik, I., Arnold, S.E., et al. (1997) Physostigmine Reversal of Scopolamine-Induced Hypofrontality. Journal of Cerebral Blood Flow & Metabolism, 17, 220-228.
https://journals.sagepub.com/doi/full/10.1097/00004647-199702000-00012#
[6]
Onishi, A. (2008) Pharmacokinetic Characteristics in the Elderly. Japanese Journal of Clinical Pharmacology and Therapeutics, 39.
https://www.jstage.jst.go.jp/article/jscpt/39/1/39_1_2/_pdf
[7]
Sakurada, T., Kawaguchi, H., Eguchi, H., Endo, K. and Tanaka, K. (2004) Evaluation of the Optimal Dose of Morphine in Cancer Pain.
http://www.jnrc.net/jnrc24/24s02.pdf
Saji, N., Niida, S., Murotani, K., Hisada, T., Tsuduki, T., Sugimoto, T., Kimura, A., Toba, K. and Sakurai, T. (2019) Analysis of the Relationship between the Gut Microbiome and Dementia: A Cross-Sectional Study Conducted in Japan. Scientific Report, 9, Article No. 1008.
[11]
Dominy, T.S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A. and Nguy, M. (2019) Porphyromonas gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors. Science Advances, 5, eaau3333.
[12]
Alonso, R., Pisa, D., Fernández-Fernández, A.M. and Carrasco, L. (2018) Infection of Fungi and Bacteria in Brain Tissue from Elderly Persons and Patients with Alzheimer’s Disease. Frontiers in Aging Neuroscience, 10, 159.
[13]
Satoru Shimizu, M.D. (2014) Scalp Neuralgia and Headache Due to Anatomical Factors of the Skull Surface. Clinical Neurology, 54-55, 387-395.
[14]
Ohfuji, M., Tsuchida, T., Nozawa, M. and Chatani, Y. (2013) Rapid Determination of Natural Toxins that Caused Food Poisoning by Liquid Chromatography with Tandem Mass Spectrometry. Annual Report, Institute of Public Health and Environmental Science, Kyoto City, Kyoto Prefecture No. 58.
http://www.pref.kyoto.jp/hokanken/documents/nenpou58_08.pdf
[15]
Arai, K., Matsuki, N., Ikegaya, Y. and Nishiyama, N. (2001) Deterioration of Spatial Learning Performances in Lipopolysaccharide Treated Mice. The Japanese Journal of Pharmacology, 87, 195-201. https://doi.org/10.1254/jjp.87.195