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The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

C. Brazell

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

C. Ward

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

P. Broks

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

M. Traub

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

S.M. Stahl

Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK

Administration of the muscarinic antagonist scopolamine has been proposed as a pharmacological model for Alzheimer's disease. We have attempted to characterize the cognitive deficits produced by the administration of scopolamine (0.2 and 0.4 mg intra muscularly) to normal volunteers. We have also demonstrated reversal of these deficits by the cholinesterase inhibitor physostigmine (1.2 mg intramuscularly). Physostigmine also elevated subjects' plasma ACTH levels, a marker of central cholinergic activity. In the cognitive study, we found that scopolamine impaired subjects' performance on verbal learning, spatial learning and choice reaction time. These changes were associated with subjective sedation as measured by analogue rating scales. Physostigmine attenuated the impairment in verbal learning and reduced subjective sedation. In the biochemical study we examined the effects of the same drug regimes on plasma ACTH levels. Physostigmine administered with a peripherally active cholinergic antagonist (glycopyrrolate 0.2 mg intramuscularly) produced a rise in ACTH level which reached a peak 30 min after drug administration. Such a rise was not apparent when the physostigmine was coadministered with scopolamine. These results suggest that cognitive and neuroendocrine indices of central cholinergic activity such as these may be useful in determining the effectiveness of potential new therapeutic agents for Alzheimer's disease.

Journal of Psychopharmacology, Vol. 2, No. 2, 67-79 (1988)
DOI: 10.1177/026988118800200202


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