A Strategy of “Combination Chemotherapy” in Alzheimer's Disease: Rationale and Preliminary Results with Physostigmine plus Deprenyl

Abstract

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.

Combination Therapy for Early Alzheimer's Disease: What Are We Waiting for?

“…Hence, the testing of efficacious and safe combinations that could further prolong optimal functioning in the earliest stages of AD and/or delay the onset of symptomatic AD is of immediate relevance. Given the multiple pathological and neurochemical deficits in AD, 1, 3, 15, 20–22 combination therapy seems logical 11, 21 . Clinical experience with diseases such as hypertension and cancer would support this argument.…”

Neuropathobiology of Senile Dementia and Mechanism of Action of Nootropic Drugs

“…The combination of selegiline + physostigmine (Sunderland et al 1992) may represent an example of combined treatment using 2 nootropics with different activity spectrum. However, the therapeutic outcome was not satisfactory, probably due to the choice of an unsuitable cholinomimetic agent.…”

Treatment of Alzheimer's disease: future directions

“…However, a placebo-controlled trial of another MAO-type-B inhibitor, milacemide, has shown no measurable benefit (43). Some researchers have taken this approach further and have simultaneously administered selegiline and physostigmine, with some preliminary success (44). Combinations of physostigmine with clonidine, tacrine, or yohimbine have also been investigated (45,46).…”