The subtype-selective nicotinic acetylcholine receptor positive allosteric potentiator 2087101 differentially facilitates neurotransmission in the brain

European Journal of Pharmacology
Giovanna de FilippiYing Chen

Abstract

Positive allosteric modulators of centrally expressed nicotinic acetylcholine receptors have therapeutic potentials in areas of cognition, motor function and reward. Several chemical classes of allosteric modulators that are selective for alpha7 nicotinic receptors have been characterised, but potentiators for the most widely expressed alpha4beta2 nicotinic receptor subtype are few and less defined, owing probably to the difficulty to achieve selectivity over other heteromeric receptor subtypes. 2087101 (2-amino-5-keto)thiazole) is a potent potentiator of both alpha7 and alpha4beta2 receptors and it has selectivity against the alpha3beta4 subtype, which may be responsible for the undesirable peripheral side effects. To further characterise its ability to differentiate between native nicotinic receptors, we examined the effects of 2087101 on alpha7, alpha4beta2* and alpha3beta4* receptor-mediated responses in the rat brain in electrophysiological and neurochemical experiments. 2087101 significantly potentiated agonist-induced, alpha7 and non-alpha7 receptor-mediated, GABAergic postsynaptic currents in cultured hippocampal neurones, but not the nicotine-stimulated [(3)H]noradrenaline release from hippocampal slices, which was pri...Continue Reading

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Citations

Mar 12, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·F J ArenzanaR Arévalo
Jun 6, 2014·Journal of Medicinal Chemistry·Li-Fang YuAlan P Kozikowski
Feb 15, 2011·Pharmacology, Biochemistry, and Behavior·Alvin V TerryScott J Webster

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