Cognition enhancers nicotinic acetylcholine receptor

Nicotine, the principal psychoactive alkaloid in tobacco, has cognitive-enhancing effects. It directly activates nicotinic acetylcholine receptors in brain areas critical for cognition, creating both acute and chronic effects. 

Anabaseine (201) Tetrahydro-pyridinyl pyridine derivative (a nicotinic compound) 3-(2,4-Dimethoxy benzylidene)-anabaseine (DMXBA GTS-21) (202) Neurology (Alzheimer s disease) Enhances cognition it acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the o4p2 and a subtypes, but activates only the a to a significant extent Phase I/II CoMentis 927-933... 

D.L., Decker, M.W., Brioni, J.D., Buckley, M.J., Rodrigues, A.D., Marsh, K.G., Anderson, D.J., Buccafusco, J.J., Prendergast, M.A., Sullivan, J.P., Williams, M., Americ, S.P., Holladay, M.W., 1997. Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmeth-oxy)pyridine (ABT-089) an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties. J. Med. Chem. 40, 385-390. 

Vernier, J.-M., El-Abdellaouri, H., Holsenback, H., Cosford, N.D.P., Bleicher, L., Barker, G., Bontempi, B., Chavez-Noriega, L., Menza-ghi, F., Rao, T.S., Teid, R., Sacaan, A.I., Suto, C., Washburn, M., Lloyd, G.K., McDonald, LA., 1999. 4-[[2-(l-Methyl-2, pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A) a novel cognitive enhancer with selectivity for neuronal nicotinic acetylcholine receptors. J. Med. Chem. 42, 1684-1686. 

Galanthamine is the only alkaloid of this class that has already found apphcation in medicine. It is approved for the symptomatic treatment of Alzheimer s disease in Europe and the United States. Its mode of action consists in a competitive and reversible inhibition of acetylcholinesterase, which leads to an increased concentration of acetylcholine at neuronal synapses. In addition, galanthamine acts as an allosteric modulator on nicotinic acetylcholine receptors. Since a characteristic featnre of Alzheimer s disease is the loss of acetylcholinergic neurons concomitant with decreased levels of acetylcholine, galanthamine can, at least partially, compensate the damage and thus enhance cognitive functions in Alzheimer s patients. 

Wallace TL, Porter R (2011) Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease. Biochem Pharmacol 82 891-903... 

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