Galanthamine and other Amaryllidaceae related alkaloids are inhibitors of α7, α4β2 and α3β4 nicotinic acetylcholine receptors
| Autor: | Felipe Moraga-Nicolás, Emilio Hormazabal, Patricio Iturriaga-Vásquez, Ana Mutis, Isabel Bermúdez-Díaz |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Agonist
Isoquinolinic alkaloids Nicotinic acetylcholine receptors 010405 organic chemistry Chemistry medicine.drug_class Voltage clamp lcsh:RS1-441 Pharmacology 01 natural sciences Acetylcholinesterase 0104 chemical sciences lcsh:Pharmacy and materia medica 010404 medicinal & biomolecular chemistry Nicotinic acetylcholine receptor chemistry.chemical_compound Nicotinic agonist Acetylcholinesterase inhibitor medicine General Pharmacology Toxicology and Pharmaceutics Receptor Acetylcholine receptor Xenopus oocytes |
| Zdroj: | Revista Brasileira de Farmacognosia, Vol 29, Iss 4, Pp 495-499 (2019) Revista Brasileira de Farmacognosia, Volume: 29, Issue: 4, Pages: 495-499, Published: 17 OCT 2019 |
| Popis: | 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. Keywords: Isoquinolinic alkaloids, Nicotinic acetylcholine receptors, Xenopus oocytes |
| Databáze: | OpenAIRE |
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