Methanesulfonyl Fluoride (MSF): A Double-Blind, Placebo-Controlled Study of Safety and Efficacy in the Treatment of Senile Dementia of the Alzheimer Type

Moss, Donald E.; Berlanga, Pablo; Hagan, Mary M.; Sandoval, Hugo; Ishida, Chiho

doi:10.1097/00002093-199903000-00003

Cited by 44 publications

(41 citation statements)

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“…Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of AChE, has recently been demonstrated to promote improvement in cognitive performance in patients with AD [124] , and it was also shown to attenuate simple learning and memory deficits in the MCAO rat model [16] . The seed extract of Cassia obtusifolia (COE), which has been found to inhibit AChE activity both in vitro and ex vivo, attenuated memory impairment induced by scopolamine or BCCAO in the passive-avoidance, Y-maze, and Morris water-maze tests in ICR mice [47] .…”

Section: Other Ache Inhibitorsmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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Section: Other Ache Inhibitorsmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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“…Thus, the robust and selective inhibition of brain AChE activity by MSF implicates the drug's potential use for treating memory deficits associated with abnormal cholinergic system. Recently, a double-blind, placebo-controlled study concluded that MSF produces significant clinical improvements in the cognitive performance of SDAT patients [29]. Such cognition enhancing effects of MSF persisted up to 8 weeks after withdrawal of the drug.…”

Section: Discussionmentioning

confidence: 99%

“…All tests were run blind, and the animal codes were revealed only at the end of the behavioral and histological analyses. In the present experiment, the 0.3 mg/kg dose of MSF, which was previously reported as efficacious in ameliorating cognitive deficits in animals [25,26,29], was used to examine the potential protective effects of MSF in stroke animals. Sixteen animals underwent MCAo surgery, while another sixteen animals underwent sham surgery; these two groups were further subdivided into animals that received either MSF or vehicle (see Fig.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Significant inhibition of AChE begins at a minimum of 50% inhibition. The drug treatment strategy was to induce AChE inhibition as strongly as possible within the first 48 h. Accordingly, 1.0 mg/kg MSF was administered, the highest dose that is tolerated without signs of toxicity, according to the dose-response curve [29], this dose produces 51.7% inhibition of the remaining active enzyme with each administration. Therefore, applying the pharmacodynamic calculations for repeated injections with enzyme replacement [44] with a half-time of 12 days in rat brain [28], it was expected that AChE inhibition at 24 h was 51.7% (minimum for a pharmacological effect) and at 48 h it was 75% inhibited.…”

Section: Drugsmentioning

confidence: 99%

“…Restoration of cognitive functions in stroke survivors has been less examined, thus we became interested in testing a pharmacological treatment that could protect against cognitive deficits in an animal model of stroke. Moss and colleagues [29] recently reported that methanesulfonyl fluoride (MSF), a very selective CNS acetylcholinesterase (AChE) inhibitor, improves cognitive performance in patients with senile dementia of the Alzheimer type (SDAT). Stroke patients display similar bcognitive performance deficitsQ termed bvascular cognitive impairmentsQ or VCI [37], which are milder (i.e., no dementia) than those seen in SDAT patients.…”

Section: Introductionmentioning

confidence: 99%

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Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

2005

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Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 F 10%) and significantly prolonged acquisition (398 F 62 s) and shortened retention (79 F 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 F 8%), they performed significantly better in the passive avoidance task (255 F 36 s and 145 F 18 s in acquisition and retention) than the vehicletreated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSFtreated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task. Published by Elsevier B.V.Theme: Disorders of the nervous system Topic: Ischemia

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An Easy, General and Practical Method for the Construction of Alkyl Sulfonyl Fluorides

Fang

Lekkala

et al. 2020

Adv Synth Catal

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A visible light‐induced reductive addition of 1°, 2° and 3° alkyl iodides to ethenesulfonyl fluoride, employing Hantzsch ester as a hydrogen source at room temperature was developed. This method featured a wide substrate scope and great functional group compatibility, providing facile and robust process to alkyl sulfonyl fluorides including enzyme inhibitors, natural products and drugs derivatives in up to 99% yield. Further derivatization of resultant aliphatic sulfonyl fluorides was also achieved through sulfur fluoride exchange (SuFEx) reactions to deliver sulfonates and sulfonamides as privileged motifs for medicinal chemistry.magnified image

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Methanesulfonyl Fluoride (MSF): A Double-Blind, Placebo-Controlled Study of Safety and Efficacy in the Treatment of Senile Dementia of the Alzheimer Type

Cited by 44 publications

References 0 publications

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats

An Easy, General and Practical Method for the Construction of Alkyl Sulfonyl Fluorides

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