Description
Tacrine is the first therapeutic launched specifically for the treatment of Alzheimer's
disease which affects four million people in the US alone. Clinically significant improvement in
cognition has been demonstrated in the patients with Alzheimer's disease. Although the
cause of Alzheimer's disease is not understood, degeneration of cholinergic neurons is
thought to be a primary factor in the development and progression of the disease. Tacrine is a
reversible acetylcholinesterase inhibitor that presumably acts centrally by elevating the
acetylcholine level in the cerebral cortex and by slowing degradation of acetylcholine from
intact cholinergic neurons. While tacrine improves the symptoms of Alzheimer's disease, the
underlining cause of the dementing process is not altered. It has also been suggested that the
beneficial effects of tacrine may be due to its multiple effects on several neurotransmitter
systems.
Description
Tacrine is a derivative of aminoacridine that functions as an inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (IC
50s = 31 and 26.5 nM, respectively). Tacrine also inhibits the uptake of serotonin and norepinephrine in rat cerebral cortex and decreases depolarization-induced calcium influx through L-type calcium channels in SN56 neuronal cells. Formulations containing tacrine have been used clinically in the treatment of Alzheimer’s disease.
Chemical Properties
Pale Yellow Solid
Uses
A potent centrally acting anticholinesterase, for therapy of memory deficits in patients with Alzheimers disease. THA also selectively blocks potassium channels in the central nervous system, which results in an increased release of acetylcholi
Uses
A potent centrally acting anticholinesterase for therapy of memory deficits in patients with Alzheimer's disease. THA also selectively blocks potassium channels in the central nervous system, which results in an increased release of acetylcholine and a prolongation of the action potential of the presynaptic cholinergic neurons.
Uses
anticholinesterase, cognitive adjuvant, K channel blocker
brand name
Cognex (Sciele).
General Description
Tacrine hydrochloride,1,2,3,4-tetrahydro-9-aminoacridine hydrochloride (THA,Cognex), is a reversible cholinesterase inhibitor that hasbeen used in the treatment of Alzheimer disease for severalyears. The drug has been used to increase the levels of AChin these patients on the basis of observations from autopsiesthat concentrations of ChAT and AChE are markedly reducedin the brain, whereas the number of muscarinic receptorsis almost normal. The use of the drug is not withoutcontroversy, as conflicting results on efficacy have been reported.The drug has been used in mild-to-moderateAlzheimer dementia.
General Description
Yellow needles (from concentrated hydrochloric acid); white powder. pH of 1.5% solution: 4.5-6. Bitter taste.
Air & Water Reactions
Water soluble.
Reactivity Profile
TACRINE HYDROCHLORIDE is incompatible with strong oxidizing agents, acid chlorides and acid anhydrides . Neutralize bases in slightly exothermic reactions.
Fire Hazard
Flash point data for TACRINE HYDROCHLORIDE are not available; however, TACRINE HYDROCHLORIDE is probably combustible.
Biological Activity
Potent cholinesterase inhibitor, a cognition enhancer in vivo .
Metabolism
Tacrine is
extensively metabolized by CYP450 to at least three metabolites. The major metabolite, 1-hydroxy-tacrine, is active. Its elimination half-life is
between 1.5 and 4 hours, with metabolites being are excreted via the urine.
References
[1] CRISMON M L. Pharmacokinetics and drug interactions of cholinesterase inhibitors administered in Alzheimer’s disease.[J]. Pharmacotherapy, 1998, 18 2 Pt 2: 47-54; discussion 79-82.
[2] MUSHTAQ AHMED. Inhibition of two different cholinesterases by tacrine[J]. Chemico-Biological Interactions, 2006, 162 2: Pages 165-171. DOI:
10.1016/j.cbi.2006.06.002[3] B. DRUKARCH J. C S J E Leysen. Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4-tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer’s disease[J]. Life sciences, 1988, 42 9: Pages 1011-1017. DOI:
10.1016/0024-3205(88)90431-6[4] MAUREEN T. MCKENNA. Novel Tacrine Analogues for Potential Use against Alzheimer’s Disease: Potent and Selective Acetylcholinesterase Inhibitors and 5-HT Uptake Inhibitors[J]. Journal of Medicinal Chemistry, 1997, 40 22: 3516-3523. DOI:
10.1021/jm970150t[5] VLADIMIR DOLEAL Stanislav T Věra Lisá. Effect of tacrine on intracellular calcium in cholinergic SN56 neuronal cells[J]. Brain Research, 1997, 769 2: Pages 219-224. DOI:
10.1016/s0006-8993(97)00711-7[6] GIACOBINI E. Invited Review Cholinesterase inhibitors for Alzheimer’s disease therapy: from tacrine to future applications[J]. Neurochemistry international, 1998, 32 5: Pages 413-419. DOI:
10.1016/s0197-0186(97)00124-1[7] GARY TIN. Tricyclic phenothiazine and phenoselenazine derivatives as potential multi-targeting agents to treat Alzheimer’s disease[J]. MedChemComm, 2015, 6 1: 1930-1941. DOI:
10.1039/c5md00274e
