NDLI: Pharmacological actions of thymol and an analogue at GABAB autoreceptors.

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Pharmacological actions of thymol and an analogue at GABAB autoreceptors.

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Pharmacological actions of thymol and an analogue at GABAB autoreceptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Parker, David As Marino, Victor Ong, Jennifer
Description	Country affiliation: Australia Author Affiliation: Parker DA ( School of Dentistry, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia.)
Abstract	GABAB autoreceptors inhibit release of GABA from GABAergic 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, (4MP) on the release of [(3) H]-GABA were examined in rat neocortical slices where the GABAergic nerves had been preloaded with [(3) H]-GABA and subsequently stimulated electrically on two occasions (S1 and S2 ). Test agents, baclofen and Sch 50911 were added to the superfusion medium prior to the second period of stimulation (S2 ). Stimulation-induced overflow (SIO) of [(3) H]-GABA as a consequence of these stimulations (SIO1 and SIO2 ) were calculated and the effects of agents determined by comparing the SIO2 /SIO1 ratio in the presence of each agent with that in control tissue. Thymol potentiated the release of [(3) H]-GABA (EC50 170 µmol/L), an action reversed by baclofen (2 µmol/L). Baclofen alone had little effect on GABA release. Release of [(3) H]-GABA was inhibited by 4MP (IC50 3 µmol/L) and this effect was blocked by Sch 50911 (10 µmol/L). Alone, Sch 50911 markedly potentiated the release of GABA. These results imply that 4MP is an agonist of GABAB autoreceptors; however, further studies are needed to confirm that thymol is indeed a GABAB 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 4MP 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.
File Format	HTM / HTML
ISSN	03051870
Issue Number	9
Volume Number	41
e-ISSN	14401681
Journal	Clinical and Experimental Pharmacology and Physiology
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2014-09-01
Publisher Place	Australia
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Physiology Discipline Pharmacology Autoreceptors Agonists Antagonists & Inhibitors Gaba-b Receptor Antagonists Pharmacology Receptors, Gaba-b Metabolism Thymol Gamma-aminobutyric Acid Secretion Animals Baclofen Butylated Hydroxytoluene Analogs & Derivatives Chemistry Dose-response Relationship, Drug Gaba Agonists Male Morpholines Neocortex Drug Effects Phenols Rats Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Pharmacology

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