Combined nicotinic and muscarinic blockade in elderly normal volunteers: cognitive, behavioral, and physiologic responses

Abstract

Establishing a pharmacologic model of the memory deficits of Alzheimer's disease could be an important tool in understanding how memory fails. We examined the combined effects of the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine in eight normal elderly volunteers (age 61.9 +/- 8.3 yrs, SD). Each received four separate drug challenges (scopolamine (0.4 mg i.v.), mecamylamine (0.2 mg/kg up to 15 mg PO), mecamylamine + scopolamine, and placebo). There was a trend toward increased impairment in explicit memory for the mecamylamine + scopolamine condition as compared to scopolamine alone. Increased impairment was also seen for the mecamylamine + scopolamine condition as compared to scopolamine alone in selected behavioral ratings. Pupil size increased when mecamylamine was added to scopolamine, while systolic blood pressure and pulse changed in concordance with ganglionic blockade. These data together with previous brain-imaging results suggest that this muscarinic-nicotinic drug combination may better model Alzheimer's disease than either drug alone.