Main author: Natalia Magdalena Kowal
Institution or Company: University of Iceland
Co-Authors, Institution or Company:
Elín Soffía Ólafsdóttir, University of Iceland.
Introduction: Galanthamine, a plant alkaloid isolated from snowdrop (Galanthus sp.), is approved as a drug for treatment of mild-to-moderate Alzheimer’s disease. Galanthamine works primarily as an acetylcholinesterase inhibitor but it is also commonly referred to as a positive allosteric modulator (PAM) of neuronal nicotinic acetylcholine receptors (nAChR). Previous experiments that showed galantamine as a PAM at nAChR were primarily conducted on rat hippocampal neurons, PC12 cells naturally expressing nAChRs and in HEK cells transfected with nAChR subunits. Data available from receptors expressed in Xenopus oocytes are limited and show marginal PAM activity. The aim of the study was to answer the question: Is galantamine really a PAM of nAChRs?
Methods: Various subtypes and stoichiometries of human neuronal nAChRs were expressed in Xenopus oocytes. Electrophysiological currents evoked by ACh alone or in combination with galanthamine were recorded using two electrode voltage clamp.
Results: Galanthamine was unable to produce significant PAM responses when tested on α7, α4β2 and α4β4 nAChRs expressed in Xenopus oocytes. However, in agreement with the literature we observed inhibition of ACh-evoked responses at high concentrations (10 – 100 µM range) which is a result of an open pore blockade.
Conclusions: Galanthamine is not a PAM of nAChRs.
