Cholinergic Strategies

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

Domino EF, Chodoff P, Corssen G (1965) Pharmacologic effects of Cl-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 6 279-291 Doraiswamy PM (2002) Non-cholinergic strategies for treating and preventing Alzheimer s disease. CNS Drugs 16 811-824... 

Doraiswamy P. M. (2002). Non-cholinergic strategies for treating and preventing Alzheimer s disease. CNS Drugs 16 811-824. 

Davidson JRT, Eord SM, Smith RD, et al Long-term treatment of social phobia with clonazepam. J Clin Psychiatry 52 (suppl) 16-20, 1991b Davidson JRT, Potts N, Richichi E, et al Treatment of social phobia with clonazepam and placebo. J Clin Psychopharmacol 13 423-428, 1993 Davies P Theoretical treatment possibilities for dementia of the Alzheimer type the cholinergic hypothesis, in Strategies for the Development of an Effective Treatment for Senile Dementia. Edited by Crook T, Gershon S. New Canaan, CT, Mark Powley Associates, 1981, pp 19-32... 

It should be noted that as these agents bear a permanently charged quaternary ammonium group they would not be expected to penetrate the blood-brain barrier. Thus, the study of the ability to inactivate central cholinergic receptors selectively and produce an Alzheimer s-like experimental dementia would have to be studied in isolated brain preparations in vitro and with the aid of push-pull cannula strategies for in vivo studies. 

THE CHOLINERGIC HYPOTHESIS OF ALZHEIMER S DISEASE AND CHOLINERGIC ENHANCEMENT STRATEGIES... 

In CONCLUSION, despite the very limited advances that have been made in developing drugs that are of real benefit to the patient with Alzheimer s disease, there have been some developments which may ultimately lead to this goal. The discovery of the defect in the forebrain cholinergic system has led to a treatment strategy which, although limited in its clinical value, raises the prospect of rational drug development. 

Auld DS, Komecook TJ, Bastianetto S, Quirion R. Alzheimer s disease and the basal forebrain cholinergic system relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002 68 209-245. 

Palliative treatment of Alzheimer s disease, the most common cause of dementia, has be the primary focus of research in cognitive enhancement. However, despite these efforts, effective pharmacological interventions remain elusive. The most fruitful pharmacological strategy pursued in AD research to date has focused on the relief of cognitive and memory deficits that are attributed to cholinergic dysfunction. 

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