Planta Med 2013; 79 - PN43
DOI: 10.1055/s-0033-1352386

Assessment of the Nav1.2 sodium channel activity of Aconitum diterpene and norditerpene alkaloids

B Borcsa 1, L Fodor 2, D Csupor 1, P Forgo 1, J Hohmann 1
  • 1University of Szeged, Institute of Pharmacognosy, Szeged, 6720, Hungary
  • 2Gedeon Richter Plc., Budapest, 1475, Hungary

Voltage-gated sodium channels in sensory neurons have been found to play a crucial role in several chronic painful neuropathies of different aethiology. Pharmacons that exhibit a use-dependent blockade of these channels, like anticonvulsants, antiarrhythmics and local anesthetics, have been proven to be useful drugs in the treatment of chronic neuropathic or inflammatory pain states, epilepsy, migraine and neurodegeneration related to ischaemia.

Aconitum species are traditionally used as painkillers, anaesthetics, cardiotonics and antirheumatic agents; characteristic compounds of these plants are the diterpenoid alkaloids. Analgesic effect of diterpene alkaloids is well-documented, and antinociception is a key component of this activity, which can develop by action on voltage-gated Na+ channels.

In the present study twenty-four C18, C19 and C20 diterpene alkaloids, representing the structural diversity of Aconitum alkaloids, were evaluated for Nav1.2 channel inhibitory activity by the whole-cell patch clamp technique. Pyroaconitine, ajacine, septentriodine, and delectinine demonstrated significant Nav1.2 channel inhibition (42.4 – 57.0%) at 10 mM concentration; several other compounds (acovulparine, acotoxicine, hetisinone, 14-benzoylaconine-8-O-palmitate, aconitine, and lycoctonine) exerted moderate activity (21.9 – 30.3%), while the rest of the tested alkaloids were considered to be inactive.

This is the first paper to report promising experimental results obtained in relation to a specific Nav1 channel subtype inhibitory activity of diterpene alkaloids. On the basis of these results and by exhaustive comparison of data of previously published QSAR studies on diterpene alkaloids, certain conclusions on the structure-activity relationships of Aconitum alkaloids concerning Nav1.2 channel inhibitory activity is proposed.

Acknowledgements: This study was supported by the European Union and co-funded by the European Social Fund (TÁMOP-4.2.2.A-11/1/KONV-2012 – 0035).