Effect of galantamine on the human α 7 neuronal nicotinic acetylcholine receptor, the Torpedo nicotinic acetylcholine receptor and spontaneous cholinergic synaptic activity

1 Various types of anticholinesterasic agents have been used to improve the daily activities of Alzheimer's disease patients. It was recently demonstrated that Galantamine, described as a molecule with anticholinesterasic properties, is also an allosteric enhancer of human α 4 β 2 neuronal nicotinic receptor activity. We explored its effect on the human α 7 neuronal nicotinic acetylcholine receptor (nAChR) expressed in Xenopus oocytes. 2 Galantamine, at a concentration of 0.1  μ M , increased the amplitude of acetylcholine (ACh)‐induced ion currents in the human α 7 nAChR expressed in Xenopus oocytes, but caused inhibition at higher concentrations. The maximum effect of galantamine, an increase of 22% in the amplitude of ACh‐induced currents, was observed at a concentration of 250  μ M Ach. 3 The same enhancing effect was obtained in oocytes transplanted with Torpedo nicotinic acetylcholine receptor (AChR) isolated from the electric organ, but in this case the optimal concentration of galantamine was 1  μ M . In this case, the maximum effect of galantamine, an increase of 35% in the amplitude of ACh‐induced currents, occurred at a concentration of 50  μ M ACh. 4 Galantamine affects not only the activity of post‐synaptic receptors but also the activity of nerve terminals. At a concentration of 1  μ M , quantal spontaneous events, recorded in a cholinergic synapse, increased their amplitude, an effect which was independent of the anticholinesterasic activity associated with this compound. The anticholinesterasic effect was recorded in preparations treated with a galantamine concentration of 10  μ M . 5 In conclusion, our results show that galantamine enhances human α 7 neuronal nicotinic ACh receptor activity. It also enhances muscular AChRs and the size of spontaneous cholinergic synaptic events. However, only a very narrow range of galantamine concentrations can be used for enhancing effects.British Journal of Pharmacology (2005) 145 , 672–678. doi: 10.1038/sj.bjp.0706221