Details

Autor(en) / Beteiligte

• Friese, Jutta
• Gleitz, Johannes
• Gutser, Ulrike T
• Heubach, Jürgen F
• Matthiesen, Theo
• Wilffert, Bob
• Selve, Norma

Titel

Aconitum sp. alkaloids: the modulation of voltage-dependent Na + channels, toxicity and antinociceptive properties

Ist Teil von

• European journal of pharmacology, 1997-10, Vol.337 (2), p.165-174

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

1997

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Alkaloids from Aconitum sp., used as analgesics in traditional Chinese medicine, were investigated to elucidate their antinociceptive and toxic properties considering: (1) binding to Na + channel epitope site 2, (2) alterations in synaptosomal Na + and Ca 2+ concentration ([Na +] i, [Ca 2+] i), (3) arrhythmogenic action of isolated atria, (4) antinociceptive and (5) acute toxic action in mice. The study revealed a high affinity group ( K i 1 μM) and a low affinity group ( K i 10 μM) of alkaloids binding to site 2. The compounds of the high affinity group induce an increase in synaptosomal [Na +] i and [Ca 2+] i (EC 50 3 μM), are antinociceptive (ED 50, 25 μg/kg), provoke tachyarrhythmia and are highly toxic (LD 50 70 μg/kg), whereas low affinity alkaloids reduce [Ca 2+] i, induce bradycardia and are less antinociceptive (ED 50 20 mg/kg) and less toxic (LD 50 30 mg/kg). These results suggest that the alkaloids can be grouped in Na + channel activating and blocking compounds, but none of the alkaloids seem to be suitable as analgesics because of the low LD 50/ED 50 values.