| Popis: |
Alzheimer’s disease (AD) is a clinically debilitating dementia associated with various stages of memory dysfunction leading ultimately over a period of years to death. Extensive research is ongoing to determine the underlying etiology of the disease process as well as potential biochemical markers (AMADUCCI et a1. 1993; WISNIEWSKI et a1. 1993). Commonly associated with a decline in cognitive function is a decrease in central cholinergic transmission (DE SOUZA 1993). This cholinergic deficit theory has led to several approaches for treating the symptoms of AD involving acetylcholine esterase (AChE) inhibitors or muscarinic agonists. In the early to mid-1980s, SUMMERS and colleagues (1981, 1986, 1989) experimented with the use of the tetrahydroacridine derivative tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate, THA, Cognex) for the treatment of AD. After extensive clinical trials, tacrine administration was shown to produce statistically significant improvements in several measures of cognitive function (FARLOW et a1. 1992; KNAPP et a1. 1994). As a result of these clinical trials, tacrine has been approved by the United States Food and Drug Administration for the treatment of mild to moderate AD. Side effects commonly associated with tacrine treatment are cholinergic in nature involving gastrointestinal discomfort (KNAPP et a1. 1994). Of more concern was the relatively high incidence (up to 50% of patients treated) of asymptomatic elevations in serum alanine aminotransferase (ALT) activity (KNAPP et al. 1994; NYBACK et al. 1993; O’BRIEN et al. 1991; ROBERTS et al. 1990; WATKINS et al. 1994). |
