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Selective changes in sensitivity to cholinergic agonists and receptor changes elicited by continuous physostigmine
R V Bhat1, S L Turner, M J Marks
1Institute for Behavioral Genetics, University of Colorado, Boulder.
The Journal of Pharmacology and Experimental Therapeutics
|October 1, 1990
Summary
Physostigmine, a potential Alzheimer's disease treatment, primarily acts centrally. While it increases nicotinic receptors, tolerance develops, questioning long-term effectiveness for Alzheimer's patients.
Area of Science:
- Neuroscience
- Pharmacology
- Neurodegenerative Diseases
Background:
- Alzheimer's disease (AD) is linked to reduced brain nicotinic receptors.
- Physostigmine, a cholinergic agonist, is a potential AD treatment.
- The comprehensive effects of physostigmine require thorough characterization.
Purpose of the Study:
- To evaluate the central and peripheral effects of physostigmine.
- To assess changes in receptor sensitivity and binding after chronic physostigmine administration.
- To determine the potential of physostigmine as a long-term therapeutic for AD.
Main Methods:
- Physostigmine's effects were tested in C57BL/6 mice using behavioral and physiological assessments.
- Receptor sensitivity to physostigmine, nicotine, and oxotremorine was examined.
- Nicotinic and muscarinic receptor binding was quantified after 10-day continuous physostigmine infusion.
Main Results:
- Physostigmine's effects, except on heart rate, were centrally mediated.
- Chronic physostigmine induced tolerance to itself and slightly reduced nicotine sensitivity.
- AChE activity was inhibited by 62%, with increased L-[3H] nicotine binding in several brain regions.
Conclusions:
- Physostigmine treatment may partially restore reduced nicotinic receptors in AD.
- Tolerance and potential functional deficits in upregulated receptors question its prolonged efficacy.
- Further research is needed to ascertain physostigmine's long-term therapeutic value in Alzheimer's disease.