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Adv Pharmacol Sci. 2012; 2012: 708178.
Published online Jan 29, 2012. doi:  10.1155/2012/708178
PMCID: PMC3272790
Effect of a CNS-Sensitive Anticholinesterase Methane Sulfonyl Fluoride on Hippocampal Acetylcholine Release in Freely Moving Rats
Tamotsu Imanishi, 1 ,2 Muhammad Mubarak Hossain, 1 ,3 Tadahiko Suzuki, 1 Ping Xu, 1 ,4 Itaru Sato, 1 and Haruo Kobayashi 1 ,5 *
1Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Ueda, Morioka 020-8550, Japan
2Department of Food Safety, Pharmaceutical and Medical Safety Bureau, Ministry of Health, Labour and Welfare, Kasumigaseki, Chiyoda, Tokyo 100-8916, Japan
3Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA
4Sciences of Cryobiosystems, United Graduate School of Agricultural Sciences of Iwate University, Ueda, Morioka 020-8550, Japan
57-272 Aza-Mukaishinden, Ukai, Takizawa-mura, Iwate-gun, Iwate Prefecture 020-0172, Japan
*Haruo Kobayashi: yhkoba/at/ictnet.ne.jp
Academic Editor: Karim A. Alkadhi
Received August 30, 2011; Revised October 25, 2011; Accepted October 25, 2011.
Abstract
Anticholinesterases (antiChEs) are used to treat Alzheimer's disease. The comparative effects of two antiChEs, methanesulfonyl fluoride (MSF) and donepezil, on the extracellular levels of ACh in the hippocampus were investigated by in vivo microdialysis in freely moving rats. MSF at 1 and 2 mg/kg produced a dose-dependent increase in ACh efflux from 10 min to at least 3 hrs after injection. At 2 mg/kg, the increase was still present at 24 hr. Donepezil at 1 mg/kg showed a similar but smaller effect, and, paradoxically, 2 mg/kg showed no consistent effect. MSF at 1 and 2 mg/kg decreased acetylcholinesterase activity in the hippocampus to 54.8 and 20.1% of control, respectively. These results suggest that MSF is a suitable candidate for the treatment of Alzheimer's disease.
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