Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of safety and efficacy in the treatment of senile dementia of the Alzheimer type.

Abstract

The purpose of the present study was to evaluate methanesulfonyl fluoride (MSF), a very long-acting CNS-selective acetylcholinesterase (AChE) inhibitor, as a palliative treatment for senile dementia of the Alzheimer type (SDAT). In experiment I, MSF (0.03-0.18 mg/kg) was administered orally to 10 normal volunteers to measure toxicity and establish dose/response function in erythrocyte AChE. MSF produced a dose-response function of %inhibition = (40)(Log10[MSF mg/kg] + 51.7) with no toxicity at these doses. Experiment II was a 16-week double-blind, placebo-controlled study of the safety and efficacy of MSF in doses of up to 0.18 mg/kg given three times per week in 5 men and 10 women (60-82 years), with Mini-Mental State Examination (MMSE) scores of 9-24, who had SDAT. MSF produced a mean of 89.5% inhibition of erythrocyte AChE in patients and improved cognitive performance as measured by the MMSE, Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-COG), Global Deterioration Scale, and the Clinical Interview Based Impression of Change (CIBIC). Most of the improvement on the ADAS-COG was maintained 8 weeks after ending MSF. No patients left the study because of drug-related adverse events and there were no toxic effects. MSF may be a safe and effective palliative treatment for SDAT and further clinical trials in larger groups of patients are warranted.

• Authors: D E Moss, P Berlanga, M M Hagan, H Sandoval, C Ishida
• Journal: Alzheimer disease and associated disorders (Alzheimer Dis Assoc Disord) Vol. 13 Issue 1 Pg. 20-5 (Jan 1999) ISSN: 0893-0341 [Print] United States
• PMID: 10192638 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinesterase Inhibitors
• Sulfones
• methanesulfonyl fluoride
• Acetylcholinesterase

Topics

• Acetylcholinesterase (drug effects, metabolism)
• Administration, Oral
• Adult
• Alzheimer Disease (drug therapy, pathology)
• Cholinesterase Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Cognition (drug effects)
• Dementia (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Palliative Care
• Sulfones (administration & dosage, pharmacology, therapeutic use)
• Treatment Outcome