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Effects of metrifonate, a long‐acting cholinesterease inhibitor, in alzheimer disease: Report of an open trial
Author(s) -
Becker Robert E.,
Colliver Jerry,
Elble Rodger,
Feldman Eleanor,
Giacobini Ezio,
Kumar Vinod,
Markwell Stephen,
Morieatry Pamela,
Parks Randolph,
Schillcutt Samuel D.,
Unni Latha,
Vicari Sandra,
Womack Cindy,
Zec Ronald F.
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430190407
Subject(s) - cholinesterase , acetylcholinesterase , medicine , cholinergic , pharmacology , open label , acetylcholinesterase inhibitor , tacrine , central nervous system , clinical trial , endocrinology , chemistry , enzyme , biochemistry
This is the first study of a multiple‐dose trial of metrifonate (Met), a long‐acting cholinesterase (ChE) inhibitor, conducted over a prolonged period of time in humans. We have administered Met to 20 patients who met NINCDS‐ADRDA criteria for probable Alzheimer disease (AD). Patients were given, under open conditions, single oral doses of Met. 2.5, 5, 7.5, and 15 mg/kg/wk. A statistically significant improvement in the Alzheimer Disease Assessment Scale (ADAS) scores was observed with the 5 mg/kg/wk dose. Maximal improvement on the ADAS was associated with a mean 55.9% (± 12.6% standard deviation) activity level of red blood cell (RBC) acetylcholinesterase (AChE). Over 80% inhibition of plasma and RBC ChE was achieved with only minor side effects. Cholinesterate inhibition in the CSF of two patients was 37% and 47.5% 24 hr after a second dose of 5 mg/kg/wk of Met separated by 7 days from the first dose. Twenty‐seven minor side effects were reported: none on 2.5 mg, 5 on 5 mg, 9 on 7.5 mg, and 13 on the 15 mg dose. None of the side effects was clinically significant or drug related or required termination of treatment of dosage adjustment. We conclude that Met is a useful pharmacological probe of cholinergic function in the central nervous system and that double‐blind evaluation of Met in AD is warranted.