Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of safety and efficacy in the treatment of senile dementia of the Alzheimer type.
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.
Moss
D E
DE
Department of Psychology, University of Texas at El Paso, 79968-0553, USA. dmoss@utep.edu
Berlanga
P
P
Hagan
M M
MM
Sandoval
H
H
Ishida
C
C
D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D013450:Sulfones; C005109:methanesulfonyl fluoride; D000110:Acetylcholinesterase