Tacrine

Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist. Tacrine hydrochloride hydrate is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC50s of 31 nM and 25.6 nM, respectively.

Tacrine hydrochloride is an inhibitor of three different hepatic microsomal cytochrome P-450 enzyme sub-families. Tacrine hydrochloride at 40 mg/mL, 80 mg/mL or 200 mg/mL inhibits 3-hydroxymethyl antipyrine (HMA) production by 17%, 24% and 41% and OHA production by 52%, 55% and 79%, respectively, in hepatic microsome. [1] Tacrine severely inhibits normal levels of secretion of soluble APP derivatives by cells into conditioned media in glial, fibroblast, pheochromocytoma (PC12), and neuroblastoma cells. Tacrine treatment does not alter the level of HSP-70 in cell extracts and tacrine affected mildly the secretion of PN-1 in neuroblastoma and PC12 cells. [2] Tacrine (1 μM) attenuates the neurotoxic effect of A beta(25-35) in rat PC12 cells. [3]

Tacrine (3 mg/kg, i.p.) prevents the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response in mice. [4] Tacrine (5mg/kg) shows significant effects of the inhibition of brain AChE for more than 6 hours in the rat hippocampus. Tacrine (5mg/kg) increases acetylcholine concentration in the synaptic cleft of the hippocampus mostly through AChE inhibition in the rat hippocampus, and the maximum increases are observed at about 1.5 hours. [5]

[1] Danbury TC, et al. Eur J Drug Metab Pharmacokinet, 1999, 24(1), 91-96. [2] Lahiri DK, et al. J Neurosci Res, 1994, 37(6), 777-787. [3] Svensson AL, et al. Neuroreport, 1998, 9(7), 1519-1522.