Tacrine (Tetrahydroaminacrine, Tetrahydroaminoacridine) is a centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. It also acts as a histamine N-methyltransferase inhibitor.
Tacirne is an active cholinesterase inhibitor that blocks the degradation of cholinergic nerves in the cerebral cortex and hippocampus to increase cholinergic transmission. Tacrine induces hepatic damages in vitro. It can also induce oxidative stress and mitochondrial dysfunction. Tacrine treatment in HepG2 cells markedly inhibits the phosphorylation of GSK3β[1].
In rats, tacrine increased markers of liver damages (ALT and AST), degenerative region areas, and numbers of infiltrating inflammatory cells. Tacrine is known to induce hepatocyte necrosis and degeneration[1]. In the past, tacrine was used for the treatment of cognitive dysfunction during vascular dementia and Alzheimer disease. It is found to abolish lipopolysaccharide induced inflammation including IL-6 secretion in the central nervous system. Tacrine can aggravate the progress of tularemia in a mouse model--the effect would be beneficial in several pathologies such as neurodegenerative disorders; e.g. the positive effect of tacrine when used in therapy for Alzheimer's disease would be attributed to its anti-inflammatory action in addition to any improvement in cognitive functions[2].
[1] Park SM, et al. Biol Pharm Bull. 2015, 38(2):184-92. [2] Miroslav Pohanka, et al. Journal of Applied Biomedicine. 2013, 11(3)：187-193. [3] Cumming P, et al. Biochem Pharmacol. 1992, 44(5):989-92.