Abstract
Alzheimer’s disease (AD) is a complex and multifaceted neurodegenerative disease characterized by cognitive and behavioral abnormalities. The primary cognitive deficit has been correlated with extensive cholinergic dysfunction and the efficacy of cholinergic therapies in this disease validates and supports the cholinergic hypothesis of AD (Weinstock, 1995). To date, tacrine has shown clinical efficacy in 20 to 30% of AD patients and remains the only acetylcholinesterase inhibitor (AChEI) to receive FDA approval for symptomatic treatment (Knapp et al., 1994). However, the limited efficacy of pure cholinergic therapies suggests that other neurochemical deficiencies are involved.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bondareff W, Mountjoy CQ and Roth M (1982): Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32:164–168.
Bondareff W, Mountjoy CQ, Roth M, Rossor MN, Iversen LL, Reynolds GP and Hauser DL (1987): Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer Disease. Alz Dis Assoc Disor 1:256–62.
Burke WJ, Roccaforte WH, Wengel SP, Bayer BL, Ranno AE and Willcockson NK: L-Deprenyl in the treatment of mild dementia of the Alzheimer type: results of a 15-month trial. J Am Geriatr Soc 41:1219–1225.
Camacho F, Smith CP, Vargas HM and Winslow JT (1996): α2-Adrenoceptor antagonists potentiate acetylcholinesterase inhibitor effects on passive avoidance learning in the rat. Psychopharmacol 124 (in press).
Cuadra G and Giacobini E (1995): Coadministration of Cholinesterase inhibitors and idazoxan: effects of neurotransmitters in rat cortex in vivo. J Pharmacol Exp Ther 273:230–240.
Cutler NR, Haxby J, Kay AD, Narang PK, Lesko LJ, Costa JL, Ninos M, Linnoila M, Potter WZ, Renfrew JW and Moore AM (1985): Evaluation of zimeldine in Alzheimer’s Disease. Arch Neurology 42:744–748.
Decker MW and McGaugh JL (1991): The role of interactions between cholinergic systems and other neuromodulatory systems in learning and memory. Synapse 7:151–168.
DeMey J and Vanhoutte PM (1981): Uneven distribution of postjunctional alphar and alpha2-like adrenoceptors in canine arterial and venous smooth muscle. Circ Res 48:875–884.
Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI and the Tacrine Study Group (1994): A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. J Am Med Assoc 271:985–991.
Sara SJ and Devauges V (1989): Idazoxan, an α2-antagonist, facilitates memory retrieval in the rat. Behav Neural Biol 51:401 -411.
Smith CP, Petko WW, Kongsamut S, Roehr JE, Effland RC, Klein JT and Huger FP: Mechanisms for the increase in electrically stimulated [3H]norepine-hrine release from rat cortical slices by N-(n-propyl)-N-(4-pyridinyl)-lH-indol-l-amine. Drug Dev Res 32:13–18.
Weinstock M (1995): The pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesis: an update. Neurodegeneration 4:349–356.
Winslow JT and Camacho F (1995): Cholinergic modulation of a decrement in social investigation following repeated contacts between mice. Psychopharmacol 121:164–172.
Zubenko GS, Mossy J and Kopp U (1990): Neurochemical correlates of major depression in primary dementia. Arch Neurology 47:209–214.
Zweig RM, Ross CA, Hedreen JC, Steele C, Cardillo J, Whitehouse PJ, Folstein MF and Price DL (1988): The neuropathology of aminergic nuclei in Alzheimer’s Disease. Ann Neurology 24:233–242.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Birkhäuser Boston
About this chapter
Cite this chapter
Vargas, H.M. et al. (1997). P11467: An Orally-Active Acetylcholinesterase Inhibitor and α2-Adrenoceptor Antagonist for Alzheimer’s Disease. In: Becker, R.E., Giacobini, E., Barton, J.M., Brown, M. (eds) Alzheimer Disease. Advances in Alzheimer Disease Therapy. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4116-4_37
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4116-4_37
Publisher Name: Birkhäuser Boston
Print ISBN: 978-1-4612-8660-8
Online ISBN: 978-1-4612-4116-4
eBook Packages: Springer Book Archive