COMBINED NICOTINIC AND MUSCARINIC BLOCKADE IN ELDERLY NORMAL VOLUNTEERS - COGNITIVE, BEHAVIORAL, AND PHYSIOLOGICAL-RESPONSES

Establishing a pharmacologic model of the memory deficits of Alzheimer 's disease could be an important tool in understanding how memory fail s. We examined the combined effects of the muscarinic antagonist scopo lamine and the nicotinic antagonist mecamylamine in eight normal elder ly volunteers (age 61.9 +/- 8.3 yrs, SD). Each received foul separate drug challenges (scopolamine (0.4 mg IV), mecamylamine (0.2 mg/kg up t o 15 mg PO), mecamylamine + scopolamine, and placebo). There was a tre nd toward increased impairment in explicit memory for the mecamylamine + scopolamine condition as compared to scopolamine alone. Increased i mpairment was also seen for the mecamylamine + scopolamine condition a s compared to scopolamine alone in selected behavioral ratings. Pupil size increased when mecamylamine was added to scopolamine, while systo lic blood pressure and pulse changed in concordance with ganglionic bl ockade. These data together with previous brain-imaging results sugges t that this muscarinic-nicotinic drug combination may better model Alz heimer's disease than either drug alone. Published by Elsevier Science Inc.