A clinical comparison of tacrine (THA) and placebo was performed in 15 Alzheimer 
patients using a double blind crossover technique over 4 plus 4 weeks with one 
drug-free week in between. Treatment results, as evaluated by clinical rating 
scales and neuropsychological tests, were mostly negative. Side effects were 
few, except for elevation liver enzymes which occurred in one third of the 
patients. CSF levels of the monoamine metabolites HVA and 5-HIAA increased on 
tacrine as evidence for activation of dopamine and serotonin pathways through 
cholinergic receptors. Pharmacokinetic investigations showed that the oral 
bioavailability of tacrine was low and greatly varying between subjects. 
Patients with high bioavailability of the drug tended to improve more, and also 
to have more liver enzyme elevations, than those with low bioavailability. A gel 
preparation for rectal administration was manufactured for comparison of plasma 
levels attained during one week's treatment with levels attained with oral 
capsules. Preliminary results indicate that the dose of tacrine can be reduced 
to 50 per cent when administered rectally, probably as by this route the rapid 
first-pass metabolism of the drug in the liver is diminished. A clinical trial 
of tacrine via the rectal route would be justified as this could decrease the 
number of patients with liver side effects and increase the number of patients 
improving on the treatment.