Cholinergic Basis for Alzheimer Therapy by Robert E. Becker (auth.), Robert Becker, Ezio Giacobini PDF

By Robert E. Becker (auth.), Robert Becker, Ezio Giacobini (eds.)

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0 ~~ 100 ~ 100 a: 0.. '- 120 AChE 0 ~80 80 ~ 60 Placebo Physostigmine 60Placebo Physostigmine FIGURE 4. 46 mg/dose, 6 times a day at 2 hour intetvals, CSF sampled 30 min. v. 6 mg/br for 6-8 hours for 6-14 days, CSF sampled 4 hr. after start of the days infusion. Clearly the development of physostigmine analogues with improved pharmacokinetic and pharmacodynamic properties would be useful in the experimental treatment of AD. There is considerable scope for the modification of the carbamate moiety of physostigmine whilst retaining anticholinesterase activity (Atack et al, 1989).

Suzuki T, Kashima Y and Kawashima K (1989): Hemicholinium-3-resistant choline uptake system linked to acetylcholine synthesis in the rat hippocampus. Neuroscience Letts 105:211-214. Szerb JC (1978): Characterization of presynaptic muscarinic receptors in central cholinergic neurons. In: Cholinergic Mechanisms and Psychophannacology, Jenden DJ, ed. New York: Plenum Press, pp. 49-60. Taylor P (1990): Anticholinesterase agents. In: The Phannacological Basis of Therapeutics, Gilman AG, Rail TW, Nies AS and Taylor P, eds.

Convemely, in AD, and in demented Parkinson's disease patients, there is a selective loss of the 04 fonn of AChE (Atack, 1991). A similar loss of the 04 fonn of hippocampal AChE following lesions of the rat septo-hippocampal pathway is consistent with the 04 fonn of cortical AChE being primarily localized on presynaptic cholinergic nerve tenninals. In AD, the distribution of AChE Cholinesterases in Degenerative Diseases 33 molecular fonns in the NbM is, however, unaltered (Atack, 1991), indicating that the biosynthesis of the different molecular fonns is relatively nonnal in the remaining basal forebrain neurons.

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