On the mechanism by which newly synthesized xanthone derivatives cause
conduction blockade of the rat sciatic nerve
-
1
Universidade do Porto, Instituto de Ciencias Biomedicas de Abel Salazar, Portugal
Newly synthesized chiral xanthone derivatives (CXD) from L-Valinol (XEVOL), L-Leucinol (XEL) and S-(-)-α-4- dimethylbenzylamine (XEA) are structurally very similar to local anaesthetics [1,2], to which they might share common molecular targets regarding their activity in the nervous system (e.g. anti-epileptic and anti- depressant potential). This prompted us to investigate whether these compounds exhibit anaesthetic-like properties at the neuronal cell level, focusing on their ability to block the rat sciatic nerve conduction [3]. Nerve conduction blockade might result from a selective interference with Na+ ionic currents or from a non-selective modification of membrane stabilizing properties. Thus, we also evaluated the ability of xanthone derivatives to prevent hypotonic haemolysis [4], given that erythrocytes are non-excitable cells that are devoid of voltage- gated Na+ channels.
Xanthone derivatives (XEVOL, XEA and XEL) and the core nucleus, CMX, were about equipotent regarding blockade of the rat sciatic nerve conduction, when these compounds were applied in the low micromolar concentration range (0.100-3 μM). However, at this concentration range, xanthone derivatives had little or no protective effect against hypotonic haemolysis; protection of hypotonic haemolysis was observed only when XEVOL, XEL and CMX were used in higher micromolar (30-100 μM) concentrations. It is worth noting that XEA (100 μM) was virtually devoid of the anti-haemolytic effect.
Data suggest that nerve conduction blockade caused by newly synthesized xanthone derivatives might result predominantly from an action on Na+ ionic currents. This effect can be dissociated from their ability to stabilize cell membranes, which only became apparent upon increasing the concentration of the xanthone derivatives to the high micromolar range.
This work was supported by FCT (I&D, nº226/2003; I&D, nº4040/2007), FEDER, POCI, U. Porto, and Caixa Geral de Depósitos.
References
1. Pinto et al (2005), Curr Med Chem, 12, 2517-2538;
2. Jastrebska-Wiesek et al (2003), Pol J Pharmacol, 55, 461-465;
3. Mert et al (2003), Pharmacology, 69, 68-73.
4. Seeman & Weinstein (1966), Biochem. Pharmac., 15, 1737-1752.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuronal Communication
Citation:
Leitao
L,
Pozzi
A,
Noronha-Matos
JB,
Pinto
A,
Teixeira
I,
Fernandes
C,
Melo-Pinto
P,
Oliveira
L and
Correia-de-Sa
P
(2009). On the mechanism by which newly synthesized xanthone derivatives cause
conduction blockade of the rat sciatic nerve.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.160
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:
12 Aug 2009;
Published Online:
12 Aug 2009.
*
Correspondence:
L. Leitao, Universidade do Porto, Instituto de Ciencias Biomedicas de Abel Salazar, Porto, Portugal, lp.leitao@ineb.up.pt