Voltage protocols for the identification of distinct types of sodium channel inhibitors
-
1
Institute of Experimental Medicine, Department of Pharmacology, Hungary
In order to establish a structure – activity relationship for a group of compounds, it is essential that the binding site is the same for all investigated drugs. This condition is unmet in the case of sodium channel inhibitors, where mutagenesis studies showed binding sites to be either only partially overlapping, or – for some drugs – clearly different. Sodium channel inhibitors also differ in the properties of inhibition (such as resting- and inactivated-state affinity, state-dependence, use-dependence, onset and offset kinetics, reversibility), as it has been shown in our recent study. We believe, therefore, that conventional screening for sodium channel inhibitor activity is a misguided approach, and we aimed to develop protocols which provide information not only on potency, but also on the mode of action of individual compounds. We recorded more than forty individual parameters, and used them to derive further parameters, which could give a low redundancy, high information content characterization of inhibition, while not requiring more time or cost than a conventional measurement of potency. The method is adaptable to automated patch clamp systems. We presume that determination of multiple aspects of inhibition will help to understand structure – activity relationship for sodium channel inhibitors, and to design sodium channel inhibitor drugs for specific therapeutic applications.
Keywords:
Neurophysiology,
Neuroscience
Conference:
13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011.
Presentation Type:
Abstract
Topic:
Neurophysiology
Citation:
Pesti
K,
Sas
B and
Mike
A
(2011). Voltage protocols for the identification of distinct types of sodium channel inhibitors.
Front. Neurosci.
Conference Abstract:
13th Conference of the Hungarian Neuroscience Society (MITT).
doi: 10.3389/conf.fnins.2011.84.00017
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
03 Mar 2011;
Published Online:
23 Mar 2011.
*
Correspondence:
Dr. K. Pesti, Institute of Experimental Medicine, Department of Pharmacology, Budapest, Hungary, pesti.kriszti@gmail.com