Abstract
Among the multiple transmitter deficits which have been described in Alzheimer’s Disease (AD), the degeneration of brain cholinergic cell bodies is the most sensitive, specific and severe, as indicated by the good correlation between the cholinergic pathology and dementia. Therefore, current drug development strategies in AD therapy focus on the enhancement of cholinergic neurotransmission. The most advanced class of compounds in this respect are cholinesterase (ChE) inhibitors which aim to restore the concentration of acetylcholine (ACh) in the synaptic cleft.
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
Becker RE and Giacobini E (1988): Mechanisms of Cholinesterase inhibition in senile dementia of the Alzheimer type: clinical, pharmacological, and therapeutic aspects. Drug Dev Res 12:163–195.
Becker RE, Moriearty P, Surbeck R, Unni L, Varney A and Vicari SK (1994): Second and third generation Cholinesterase inhibitors: clinical aspects. In: Alzheimer Disease: Therapeutic Strategies, Giacobini E and Becker R, eds. Boston: Birkhäuser, pp. 172–178.
Blokland A, Hinz V and Schmidt BH (1995): Effects of metrifonate and tacrine in the spatial Morris task and modified Irwin test: Evaluation of the efficacy/safety profile in rats. Drug Dev Res 36:166–179.
Hinz V, Grewig S and Schmidt BH (1996a): Metrifonate induces Cholinesterase inhibition exclusively via slow release of dichlorvos. Neurochem Res, in press.
Hinz V, Grewig S and Schmidt BH (1996b): Metrifonate and dichlorvos: Effects of a single oral administration on Cholinesterase activity in rat brain and blood. Neurochem Res, in press.
Holmstedt B, Nordgren I, Sandoz M and Sundwall A (1978): Metrifonate: Summary of toxicological and pharmacological information available. Arch Toxicol 41:3–29.
Kronforst MA, Moriearty PL, Ralphs M, Becker RE, Schmidt B, Thompson LT and Disterhoft JF (1995): Facilitation of learning in the aging rabbit after chronic metrifonate treatment. Soc Neurosci Abstr 21:196.
Main AR (1979): Mode of action of anticholinesterases. Pharmacol Ther 6:579–628.
Mori F, Cuadra G and Giacobini E (1995a): Metrifonate effects on acetylcholine and biogenic amines in rat cortex. Neurochem Res 20:1081–1088.
Mori F, Lai CC, Fusi F and Giacobini E (1995b): Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. Neuro Report 6:633–636.
Moriearty PL and Becker RE (1992): Inhibition of human brain and RBC acetylcholinesterase (AChE) by heptylphysostigmine (HPTL). Meth Find Clin Pharmacol 14:615–621.
Reiner E and Plestina R (1979): Regeneration of Cholinesterase activities in humans and rats after inhibition of O,O-dimethyl-2,2-dichlorovinyl phosphate. Toxicol Appl Pharmacol 49:451–454.
Soininen HS, Unni L and Shillcutt S (1990): Effect of acute and chronic Cholinesterase inhibition on biogenic amines in rat brain. Neurochem Res 15:1185–1190.
van der Staay FJ, Hinz VC and Schmidt BH (1996): Effects of metrifonate on escape and avoidance learning in young and aged rats. Behav Pharmacol 7:56–64.
Villén T, Aden-Abdi Y, Ericsson Ö, Gustafsson LL and Sjöqvist F (1990): Determination of metrifonate and dichlorvos in whole blood using gas chromatography and gas chromatography-mass spectrometry. J Chromatogr 529:309–317.
Weinstock M (1995): The pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesis: an update. Neurodegeneration 4:349–345.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Birkhäuser Boston
About this chapter
Cite this chapter
Schmidt, B.H., Hinz, V.C., Blokland, A., van der Staay, FJ., Fanelli, R.J. (1997). Preclinical Pharmacology of Metrifonate: A Promise for Alzheimer Therapy. 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_32
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4116-4_32
Publisher Name: Birkhäuser Boston
Print ISBN: 978-1-4612-8660-8
Online ISBN: 978-1-4612-4116-4
eBook Packages: Springer Book Archive