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Pharmacological actions of thymol and an analogue at GABA B autoreceptors
Author(s) -
Parker David AS,
Marino Victor,
Ong Jennifer
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12278
Subject(s) - autoreceptor , baclofen , chemistry , gabab receptor , gabaergic , agonist , thymol , antagonist , stimulation , pharmacology , stereochemistry , receptor , biochemistry , endocrinology , biology , chromatography , essential oil
Summary GABA B autoreceptors inhibit release of GABA from GABA ergic nerve terminals. Agonists of these receptors (e.g. baclofen) inhibit, whereas antagonists (e.g. (+)‐( S )‐5,5‐dimethylmorpholinyl‐2‐acetic acid; Sch 50911) enhance release of the transmitter. The actions of thymol (2‐isopropyl‐5‐methylphenol) and the structurally related compound 2‐tert‐butyl‐4‐methylphenol, (4 MP ) on the release of [ 3 H]‐ GABA were examined in rat neocortical slices where the GABA ergic nerves had been preloaded with [ 3 H]‐ GABA and subsequently stimulated electrically on two occasions (S 1 and S 2 ). Test agents, baclofen and Sch 50911 were added to the superfusion medium prior to the second period of stimulation (S 2 ). Stimulation‐induced overflow ( SIO ) of [ 3 H]‐ GABA as a consequence of these stimulations ( SIO 1 and SIO 2 ) were calculated and the effects of agents determined by comparing the SIO 2 / SIO 1 ratio in the presence of each agent with that in control tissue. Thymol potentiated the release of [ 3 H]‐ GABA ( EC 50 170 μ mol/L), an action reversed by baclofen (2 μ mol/L). Baclofen alone had little effect on GABA release. Release of [ 3 H]‐ GABA was inhibited by 4 MP ( IC 50 3 μ mol/L) and this effect was blocked by Sch 50911 (10 μ mol/L). Alone, Sch 50911 markedly potentiated the release of GABA . These results imply that 4 MP is an agonist of GABA B autoreceptors; however, further studies are needed to confirm that thymol is indeed a GABA B autoreceptor antagonist. Of interest are structural differences in these agents. Thymol has a propyl group in the ortho position relative to the phenolic hydroxyl, whereas in 4 MP this is a butyl group and the methyl group moves from position 5 to 4. Whether one or both of these changes was responsible for the above actions is unknown.