Efficacy and safety of a loading-dose regimen versus a no-loading-dose regimen of metrifonate in the symptomatic treatment of Alzheimer's disease: A randomized, double-masked, placebo-controlled trial

Clinical Therapeutics

Volumn 21, Issue 1, 1999, Pages 88-102

  Jann, Michael W ^a   Cyrus, Pamela A ^b   Eisner, Larry S ^c   Margolin, David I ^d   Griffin, Traci ^b   Gulanski, Barbara ^b  

^a MERCER UNIVERSITY   (United States)

^b BAYER CORPORATION   (United States)

^c Baumel Eisner Neuromedical Inst   (United States)

^d Private Practice   (United States)

Author keywords

Acetylcholinesterase; Alzheimer's disease; Loading dose; Metrifonate

Indexed keywords

CHOLINESTERASE INHIBITOR; DONEPEZIL; METRIFONATE; TACRINE; UNCLASSIFIED DRUG;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; CHOLINESTERASE INHIBITION; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEGENERATIVE DISEASE; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAPHY; FEMALE; HUMAN; LABORATORY TEST; LEG CRAMP; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; NEUROLOGIC EXAMINATION; ORAL DRUG ADMINISTRATION; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

EID: 0033009540     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(00)88270-3     Document Type: Article

References (29)

1. 1. Geldmacher DS, Whitehouse PJ. Evaluation of dementia. NEJM. 1996;335:330-336.
2. 2. Davies P, Maloney AJF. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976;2:1403. Letter.
3. 3. White P, Hiley CR, Goodhardt MJ, et al. Neocortical cholinergic neurons in elderly people. Lancet. 1977;1:668-671.
4. 4. Sims NR, Bowen DM, Allen SJ, et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem. 1983;40:503-509.
5. 5. Cummings JL, Kaufer D. Neuropsychiatric aspects of Alzheimer's disease: The cholinergic hypothesis revisited. Neurology. 1996;47:876-883.
6. 6. Whitehouse PJ, Price DL, Clark AW, et al. Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol. 1981;10:122-126.
7. 7. Arendt T, Bigl V, Tennstedt A, Arendt A. Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience. 1985;14:1-14.
8. 8. Coyle JT, Price DL, DeLong MR. Alzheimer's disease: A disorder of cortical cholinergic innervation. Science. 1983;219:1184-1190.
9. 9. Whitehouse PJ, Unnerstall JR, Tabaton M, Lanska DJ. Neurochemistry of dementia: Clinical pathological relationships. In: Bergener M, Reisberg B, eds. Diagnosis and Treatment of Senile Dementia, Heidelberg: Springer-Verlag; 1989:54-59.
10. 10. Farlow M, Gracon SI, Hershey LA, et al. A controlled trial of tacrine in Alzheimer's disease. For the Tacrine Study Group. JAMA. 1992;268:2523-2529.
11. 11. Davis KL, Thal LJ, Gamzu ER, et al. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. For the Tacrine Collaborative Study Group. NEJM. 1992;327:1253-1259.
12. 12. Knapp MJ, Knopman DS, Solomon PR, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA. 1994;271:985-991.
13. 13. Tiseo PJ, Rogers SL, Perdono CA, et al. The effect of cimetidine and ketoconazole on the pharmacokinetics of donepezil. Clin Pharmacol Ther. 1998;63:234-240.
14. 14. Rogers SL, Farlow MR, Doody RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology. 1998;50:136-145.
15. 15. Eagger SA, Levy R, Sahakian BJ. Tacrine in Alzheimer's disease. Lancet. 1991;337:989-992.
16. 16. Barner EL, Gray SL. Donepezil use in Alzheimer disease. Ann Pharmacother. 1998;32:70-77.
17. 17. Hinz VC, Grewig S, Schmidt BH. Metrifonate induces cholinesterase inhibition exclusively via slow release of dichlorvos. Neurochem Res. 1996;21:331-337.
18. 18. Hinz VC, Grewig S, Schmidt BH. Metrifonate and dichlorvos: Effects of a single oral administration on cholinesterase activity in rat brain and blood. Neurochem Res. 1996;21:339-345.
19. 19. Jann MW. Preclinical pharmacology of metrifonate. Pharmacotherapy. 1998;18(2Pt2):55-67.
20. 20. Hallack M, Giacobini E. Physostigmine, tacrine, and metrifonate: The effect of multiple doses on acetylcholine metabolism in rat brain. Neuropharmacology. 1989;28:199-206.
21. 21. Becker RE, Colliver J, Elble R, et al. Effects of metrifonate, a long-acting cholinesterase inhibitor, in Alzheimer disease: Report of an open trial. Drug Dev Res. 1990;19:425-434.
22. 22. Heinig R, Versavel M, Breuel HP, et al. Rapid attainment of steady-state acetylcholinesterase inhibition by administration of metrifonate loading and maintenance doses once daily in elderly volunteers. Biol Psychiatry. 1997;42(Suppl 1):94S. Poster and abstract.
23. 23. Cummings J, Cyrus P, Bieber F, et al. Metrifonate treatment of the cognitive deficits of Alzheimer's disease. Neurology. 1998;50:1214-1221.
24. 24. Morris JC, Cyrus PA, Orazem J, et al. Metrifonate benefits the cognitive, behavioral, and global function of patients with Alzheimer's disease. Neurology. 1998;50:1222-1230.
25. 25. Raskind M, Cyrus PA, Ruzicka BB, Gulanski B. The effects of metrifonate on the cognitive, behavioral and functional performance of Alzheimer's disease patients. J Clin Psychiatry. In press.
26. 26. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34:939-944.
27. 27. Folstein MF, Folstein SE, McHugh PR. "Mini-mental State." A practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res. 1975;12:189-198.
28. 28. Rosen WG, Terry RD, Fuld P, et al. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980;7:486-488.
29. 29. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 1994.