Abstract
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 α7, α3β4, (α4)2(β2)3 and (α4)3(β2)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 α7 were significantly more sensitive to inhibition (17 ± 0.6 µM) than the heteromeric receptor, α3β4 (90 ± 3.4 µM). Neither haemanthamine nor tazettine were more potent than
galanthamine.