Galanthamine and other Amaryllidaceae related alkaloids are inhibitors of α7, α4β2 and α3β4 nicotinic acetylcholine receptors

Galanthamine is an Amaryllidaceae-derived acetylcholinesterase inhibitor used to treat memory impairment in Alzheimer's disease and vascular dementia. There is evidence that galanthamine, in addition to its effects on acetylcholinesterase, may enhance or inhibit brain nicotinic acetylcholine receptors, which could increase or decrease the therapeutic efficacy of galanthamine, respectively. Here, we evaluated the effects of galanthamine and two others Amaryllidaceae acetylcholinesterase inhibitors (haemanthamine and tazettine) analyzed by gas chromatography-mass spectrometry and identified by comparing their mass fragmentation patterns with literature and database NIST vs.2.0 on the agonist responses of brain nicotinic acetylcholine receptors alpha 7, alpha 3 beta 4, (alpha 4)(2)(beta 2)(3) and (alpha 4)(3)(beta 2)(2). Using nicotinic acetylcholine receptors expressed heterologously in Xenopus oocytes, in conjunction with two-electrode voltage clamping, we found that galanthamine inhibits the function of nicotinic acetylcholine receptors assayed through a mix competitive and non-competitevely. Nicotinic acetylcholine receptor alpha 7 were significantly more sensitive to inhibition (17 +/- 0.6 mu M) than the heteromeric receptor, alpha 3 beta 4 (90 +/- 3.4 mu M). Neither haemanthamine nor tazettine were more potent than galanthamine. (C) 2019 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda.