Animal models of Alzheimer's disease: behavior, pharmacology, transplants

Physostigmine, oxotremorine, RS-86, and a combination of piracetam and lecithin, have all been studied in patients with Alzheimer's disease. Intravenous physostigmine produced a significant improvement in patients' ability to recognize words and particularly to distinguish words they had never seen before from words previously presented. A subgroup of Alzheimer's patients had a clinically meaningful improvement to treatment with oral physostigmine, with the degree of improvement correlating with the ability of oral physostigmine to increase the nocturnal secretion of cortisol. No statistically significant differences of piracetam or piracetam and lecithin, compared to placebo were noted, however, the ratio of red cell to plasma choline might be associated with treatment responsivity. The potential therapeutic efficacy of oxotremorine proved all but impossible to assess due to concomitant adverse effects, particularly dysphoria. Results with another cholinergic agonist, RS-86, will be reported. This drug appeared to be better tolerated than oxotremorine. Animals with a kianic acid induced cortical depletion of choline acetyltransferase were found to have a significant impairment in retention of a passive avoidance task, an abnormality that was readily reversible by physostigmine, oxotremorine and 4-amino-pyridine. Cysteamine, a depletor of somatostatin, also produced a comparable deficit.