ORAL PHYSOSTIGMINE IN ALZHEIMERS-DISEASE - EFFECTS ON NOREPINEPHRINE AND VASOPRESSIN IN CEREBROSPINAL-FLUID AND PLASMA

Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in person s with Alzheimer's disease (AD) the effects of an acute dose of physos tigmine in patients receiving chronic physostigmine treatment on the a ctivity of the cholinergically regulated nonadrenergic and arginine va sopressin (AVP) systems. Specifically, we estimated the effects of sus tained release oral physostigmine on central and peripheral noradrener gic and AVP systems by measuring norepinephrine (NE) and AVP in cerebr ospinal fluid (CSF) and plasma. Lumbar punctures were performed in bot h physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar st imulus of a hypertonic saline infusion also were measured. NE concentr ations in both CSF and plasma were significantly lower in the physosti gmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affec t the AVP response to hypertonic saline. Physostigmine appears to decr ease both central and peripheral noradrenergic activity in AD.