2024-03-29T08:24:53Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/123342022-06-01T12:29:59Zcom_10261_5063com_10261_5com_10261_105com_10261_1col_10261_5066col_10261_358
00925njm 22002777a 4500
dc
García, Daniel A.
author
Bujons Vilàs, Jordi
author
Vale, Carmen
author
Suñol, Cristina
author
2006-01-01
Thymol is a naturally occurring phenolic monoterpene known for its anti-microbial and anti-oxidant properties. It is used in dental practice and in anaesthetic halothane preparations. Recent studies have reported enhanced GABAA receptor-operated chloride channel activity and increased binding affinity of [3H]flunitrazepam in the presence of thymol. In the present work, we more closely examined the pharmacological action of thymol on the native GABAA receptor by using primary cultures of cortical neurons. Thymol enhanced GABA-induced (5 μM) chloride influx at concentrations lower than those exhibiting direct activity in the absence of GABA (EC50 = 12 μM and 135 μM, respectively). This direct effect was inhibited by competitive and non-competitive GABAA receptor antagonists. Thymol increased [3H]flunitrazepam binding (EC50 = 131 μM) and showed a tendency to increase [3H]muscimol binding. These results confirm that thymol is a positive allosteric modulator of the GABAA receptor. The thymol structural analogues menthol and cymene, which lack an aromatic ring or a hydroxyl group, did not affect [3H]flunitrazepam binding. Using a pharmacophoric model that includes a hydrogen bond donor group as well as an aromatic ring with two aliphatic substituents, we propose to demonstrate the molecular essential features of these compounds to interact with GABAA receptors. Thymol (0–1 mM) did not affect cellular viability.
Neuropharmacology 50(1): 25-35 (2006)
0028-3908
http://hdl.handle.net/10261/12334
10.1016/j.neuropharm.2005.07.009
Thymol
GABAA
Receptor
Receptor binding and chloride flux
Cultured cortical neurons
Cell viability
Pharmacophore model
Allosteric positive interaction of thymol with the GABA(A) receptor in primary cultures of mouse cortical neurons