Abstract
Senile dementia of the Alzheimer’s type (SDAT) is a disease that produces gross pathological changes in the brain. However, it has also been recently associated with specific changes in neurotransmitters such as somatostatin (Davies, Katzman and Terry, 1980; Rossor et al., 1980; Rogers and Morrison, 1984), amino acids (Arai, Kobayashi, Ichimiya, Kosaka and Iizuka, 1984) and acetylcholine (Davies and Maloney, 1976; Whitehouse et al., 1982). Although SDAT is not a disorder of a single neurotransmitter, deterioration of cholinergic function in the CNS appears to be correlated with dementia. For example, loss of the cholinergic system related to the nucleus basalis of Meynert (nbM) is associated with dementia in other disorders including Parkinson’s disease (Nakano and Hirano, 1984), parkinsonism-dementia complex of Guam, and boxer’s dementia (Nakano and Hirano, 1983). It is the apparent association between deterioration of the cholinergic system and dementia that is the basis for the cholinergic strategies for treating SDAT (e.g., Davies, 1981; Bartus, Dean, Beer and Lippa, 1982). In fact, physostigmine, a cholinesterase2 inhibitor that acts within the CNS as well as peripherally, has been reported to produce clinical improvement in tests with SDAT patients (e.g., Davis and Mohs, 1982; Brinkman and Gershon, 1983). This limited success has led to interest in developing a system for delivering cholinergic drugs directly into the CNS (Harbaugh, Roberts, Coombs, Saunders and Reeder, 1984) as well as the development of new long-lasting carbamate cholinesterase inhibitors that may have improved efficacy (Weinstock, Razin and Chorev, this volume).
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© 1986 Plenum Press, New York
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Moss, D.E., Rodriguez, L.A., Herndon, W.C., Vincenti, S.P., Camarena, M.L. (1986). Sulfonyl Fluorides as Possible Therapeutic Agents in Alzheimer’s Disease: Structure/Activity Relationships as CNS Selective Cholinesterase Inhibitors. In: Fisher, A., Hanin, I., Lachman, C. (eds) Alzheimer’s and Parkinson’s Disease. Advances in Behavioral Biology, vol 29. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2179-8_62
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DOI: https://doi.org/10.1007/978-1-4613-2179-8_62
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