Alzheimer s disease tacrine

Of the acetylcholinesterase inhibitors, tacrine, methoxy-tacrine, metrifonate, donepezil hydrochloride, and rivastigmine are used in the treatment of Alzheimer s disease. In 12-30% of patients with Alzheimer s disease, tacrine causes an increase in hepatic transaminase activity. Abdominal adverse effects are very frequent, for example nausea, anorexia, diarrhea. The peripheral cholinomimetic effects of tacrine occur in a very high proportion of patients, probably the majority. The hepatic effects seem to be such that the use of these new (and in some cases still experimental) drugs would not be justified in... 

Currently, two drugs have been approved for use in treating Alzheimer s disease. Tacrine and Aricept, which treat some of the associated memory loss. Both drugs function by inhibiting the reuptake of acetylcholine in neural synapses. 

Tacrine An anticholinesterase used in the treatment of Alzheimer s disease. 

Giacobini, E. (1998) Invited review cholinesterase inhibitors for Alzheimer s disease therapy from tacrine to future applications. Neuro chemistry International 32,413-419. 

Farlow MR, Lahiri DK, Poirier J, Da-vignon J, Schneider L, Hui SL. Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer s disease. Neurology 1998 50 669-677. 

Rigaud AS, Traykov L, Caputo L, Guel-fi MC, Latour F, Couderc R et al. The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer s disease. Eur J Neurol 2000 7 255— 258. 

Apolipoprotein E (APOE) Cholinesterase inhibitor (Tacrine) Susceptibility to Alzheimer s disease, increased by the epsilon-4 allele, and decreased by epsilon-2 allele (91)... 

Farlow, M.R., "Treatment Outcome of Tacrine Therapy Depends on Apolipoprotein Genotype and Gender of the Subjects with Alzheimer s Disease," Neurology, 50, 669-677 (1998). 

Langstrom B. (1997). Imaging of nicotinic and muscarinic receptors in Alzheimer s disease effect of tacrine treatment. Dement Geriatr Cogn Disord. 8(2) 78-84. 

Donepezil (Aricept). Donepezil is the second cholinesterase inhibitor approved for the treatment of dementia. Most physicians find it much easier to use than its predecessor. It can be given once a day and carries none of the risk of liver toxicity seen with tacrine. It has been shown in multiple clinical trials to delay the decline in cognitive function in patients with Alzheimer s disease. 

Tacrine is not an ester and interferes only with the choline-binding site of AChE. It is effective in alleviating symptoms of dementia in some subtypes of Alzheimer s disease. 

Nonannulated aminopyrans 22 and tetrahydrochromenes 104 were used in the synthesis of heteroanalogs 294 and 295 of tacrine 302, a cholinesterase inhibitor applied in Alzheimer s disease treatment (01BML727, 02BML2077, 04BMC2199, 05BMC1167, 06BMC8176). 

The results with the recently introduced centrally acting inhibitors of acetylcholinesterase like tacrine and rivastigmine for the treatment of Alzheimer s disease are modest at best. 

Several inhibitors of AChE have been developed for use in treating Alzheimer s disease, which requires that the drugs readily enter the CNS. These inhibitors are structurally unrelated and vary in their mechanism of inhibition, although all are reversible inhibitors. Tacrine (Cognex) is a monoamine acridine. Donepezil (Aricept) is a piperidine derivative that is a relatively specific inhibitor of AChE in the brain, with little effect on pseudo-ChE in the periphery. Galanthamine (Reminyl) is a tertiary alkaloid and phenanthrene derivative extracted from daffodil bulbs that is a reversible competitive inhibitor of AChE it also acts on nicotinic receptors. 

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