New Muscarinic Agonists with Special Emphasis on AF102B

1991 ◽  
pp. 354-362
Author(s):  
Abraham Fisher ◽  
Rachel Haring ◽  
David Gurwitz ◽  
Claire M. Fraser ◽  
Zipora Pittel ◽  
...  
Keyword(s):  
Muscarinic Agonists

Design, Synthesis, and Biological Characterization of Bivalent 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Selective Muscarinic Agonists

2001 ◽  
Vol 44 (26) ◽  
pp. 4563-4576 ◽  
Author(s):  
W. G. Rajeswaran ◽  
Yang Cao ◽  
Xi-Ping Huang ◽  
Mary Elizabeth Wroblewski ◽  
Tracy Colclough ◽  
...  
Keyword(s):  
Biological Characterization ◽  
Muscarinic Agonists ◽  
Design Synthesis ◽  
Thiadiazole Derivatives

A novel and selective class of azabicyclic muscarinic agonists incorporating an N-methoxy imidoyl halide or nitrile functionality

1992 ◽  
Vol 2 (8) ◽  
pp. 791-796 ◽  
Author(s):  
Steven M. Bromidge ◽  
Frank Brown ◽  
Frederick Cassidy ◽  
Michael S.G. Clark ◽  
Steven Dabbs ◽  
...  
Keyword(s):  
Muscarinic Agonists

Pharmacologic responses of the mouse urinary bladder

Open Medicine ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. 192-197 ◽  
Author(s):  
A. Canda ◽  
Christopher Chapple ◽  
Russ Chess-Williams
Keyword(s):  
Nitric Oxide ◽  
Urinary Bladder ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
Minor Role ◽  
Detrusor Muscle ◽  
Field Stimulation ◽  
Muscarinic Agonists ◽  
Electrical Field ◽  
M3 Receptor

AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

The effects of acetylcholine and atropine on the 22Na+ permeability of intestinal smooth muscle vesicles

1978 ◽  
Vol 56 (6) ◽  
pp. 921-925
Author(s):  
L. Spero
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Vesicles ◽  
Intestinal Smooth Muscle ◽  
Erythrocyte Ghosts ◽  
Muscarinic Agonists ◽  
Plasma Membrane Vesicles ◽  
Muscle Plasma Membrane ◽  
Whole Muscle ◽  
Kinetics Of

A technique is described which has enabled us to measure changes in 22Na+ efflux from smooth muscle plasma membrane vesicles. The resting 22Na+ efflux from these sealed vesicles showed a concentration-dependent increase in response to acetylcholine and other muscarinic agonists, in similar concentrations to those which increased 42K+ efflux in whole muscle. The kinetics of this efflux were complex and could not be described by less than three exponential processes. The response to agonists has, therefore, been characterized by measurement of the half-life of 22Na+ efflux (t1/2). The acetylcholine effect was inhibited by atropine, but unlike the situation in the whole muscle, this inhibition was noncompetitive. Tubocuraine (a nicotinic antagonist) had no effect on this acetylcholine response. Atropine has no effect by itself on the resting 22Na+ efflux, neither did tetrodotoxin or ouabain. 22Na+ efflux from erythrocyte ghosts and liposomes, prepared from lipid extracts of the smooth muscle plasma membrane, was not modified by acetylcholine or atropine.

scholarly journals Progress Report on the Canadian Multicentre Trial of Tetrahydroaminoacridine with Lecithin in Alzheimer's Disease

1989 ◽  
Vol 16 (S4) ◽  
pp. 543-546 ◽  
Author(s):  
S. Gauthier ◽  
R. Bouchard ◽  
Y. Bacher ◽  
P. Bailey ◽  
H. Bergman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Fixed Dose ◽  
Symptomatic Therapy ◽  
Muscarinic Agonists ◽  
Double Blind ◽  
Disability Rating Scale ◽  
Functional Autonomy ◽  
Disability Rating

ABSTRACT:Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

Sign in / Sign up

Export Citation Format

Share Document