A strategy of "combination chemotherapy" in Alzheimer's disease: rationale and preliminary results with physostigmine plus deprenyl.
Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer's disease, there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis. This report focuses on the concept of "combination chemotherapy" in Alzheimer's disease as the next generation of therapeutic strategies. Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1-deprenyl might be more beneficial than either agent alone. The authors outline a sample paradigm for such combination studies, report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl, and point to other possible "combination chemotherapy" strategies for future study.
Sunderland
T
T
Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, Maryland.
Molchan
S
S
Lawlor
B
B
Martinez
R
R
Mellow
A
A
Martinson
H
H
Putnam
K
K
Lalonde
F
F
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010830:Physostigmine / Q000008:administration & dosage* / Q000009:adverse effects; D012642:Selegiline / Q000008:administration & dosage* / Q000009:adverse effects
D012642:Selegiline; D010830:Physostigmine