IJUP08 - Universidade do Porto

Conduction block in isolated rat sciatic nerve by chiral
aminoalkanolic derivatives of xanthones
Bernardo Matos 1 , Angelo Pozzi 1 , Ana Pinto 2,3 , Inês Teixeira 2,3 , Emidio Fernandes 1 , David
Moreira 1 , Carla Fernandes 2,3 , Laura Oliveira 1 , Madalena Pinto 2,3 & Paulo Correia-de-
Sá 1
1Laboratory of Pharmacology and Neurobiology, UMIB, Institute for Biomedical Sciences of Abel
Salazar (ICBAS), 2 Research Centre of Organic Chemistry, Phytochemistry and Pharmacology of
the University of Porto (CEQOFFUP), Faculty of Pharmacy; 3 Department of Organic Chemistry,
Faculty of Pharmacy, University of Porto, Portugal.
The chemical family of xanthone derivatives was described to be one group of compounds
with a broad spectrum of biological activities [1]. In fact, it has been demonstrated that
some chiral aminoalkanolic derivatives of xanthones possess potential antiepileptic and
antidepressant activities, however, their mechanism of action at the neuronal cell level is
largely unknown [2]. This prompted us to synthetise new chiral alaninol xanthone
derivates and to evaluate their pharmacological activity in the nervous system. Since, these
coumpounds can potentially act as modulators of Na + ionic currents, their neurologic
activity was evaluated on the nerve conduction properties of rat sciatic nerve.
Electrophysiological experiments were carried out on sciatic nerves isolated from Wistar
rats (200-250 g). We used a simple extracellular partition recording technique for
monitoring chiral alaninol xanthone derivates-induced changes in membrane polarization
and evoked potential amplitudes in sciatic nerve preparations [3]. Sciatic nerves were
stimulated supramaximally with 0.05 ms duration square-wave pulses delivered at a
frequency of 0.2 Hz (Tonic stimulation). Chiral alaninol xanthone derivates were applied
during 30 minutes and their influence on nerve compound action potentials (CAP) were
recorded. All CAP parameters (amplitude, half width, and depolarization time) were
analysed. CAP parameters induced by test drugs were reported as a percentage of the
control values (in the presence of Tyrode’s solution).
CAP amplitude, half width and depolarization time observed in control conditions were
9.4±4 mV (n=3), 0.69±0.05 ms (n=3), 1.28±0.04 ms (n=3), respectively. Chiral alaninol
xanthone derivates (XEVOL and XEA, 0.100-10 μM) increased nerve conduction block, in
a concentration-dependent manner. When applied in a concentration of 1 µM, XEVOL and
XEA decreased sciatic nerve conduction by 68±11% (n=3) and by 40±21% (n=2),
respectively. Pre-treatment with XEVOL did not significantly (P>0.05) change both the
depolarization time (19±13%, n=2) and the half width (17±12%, n=2), even when the
highest concentration (10 μM) was used.
Nerve conduction block may indicate that chiral alaninol xanthone derivates possess
membrane stabilizing properties, probably by decreasing Na + ionic currents. Among the
xanthone derivates tested, XEVOL was more potent than XEA. Whether these compounds
have potential for treating epileptic seizures, neuropathic pain and/or bipolar disorders
requires further investigation.
[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.
This work was supported by University of Porto / Caixa Geral de Depósitos.
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