NDLI: Gabaergic Pharmacological Activity of Propofol Related Compounds as Possible Enhancers of General Anesthetics and Interaction with Membranes

Content Provider	Springer Nature Link
Author	Reiner, G. N. Delgado Marín, L. Olguín, N. Sánchez Redondo, S. Sánchez Borzone, M. Rodríguez Farré, E. Suñol, C. García, D. A.
Copyright Year	2013
Abstract	Phenol compounds, such as propofol and thymol, have been shown to act on the GABA$_{A}$ receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABA$_{A}$ receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [$^{3}$H]flunitrazepam with EC$_{50}$ values in the micromolar range and to increase the GABA-evoked Cl$^{−}$ influx in a concentration-dependent manner, both effects being inhibited by the competitive GABA$_{A}$ antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABA$_{A}$ receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [$^{3}$H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.
Starting Page	515
Ending Page	525
Page Count	11
File Format	PDF
ISSN	10859195
Journal	Cell Biochemistry and Biophysics
Volume Number	67
Issue Number	2
e-ISSN	15590283
Language	English
Publisher	Springer US
Publisher Date	2013-03-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	GABA$_{A}$ receptor Chloride uptake Carvacrol Eugenol Chlorothymol Membrane fluidity Biochemistry Pharmacology/Toxicology Biotechnology Cell Biology Biophysics and Biological Physics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Biochemistry Biophysics

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