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

Abstract

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 Ca2+ concentration ([Na+]i, [Ca2+]i), (3) arrhythmogenic action of isolated atria, (4) antinociceptive and (5) acute toxic action in mice. The study revealed a high affinity group (Ki 1 microM) and a low affinity group (Ki 10 microM) of alkaloids binding to site 2. The compounds of the high affinity group induce an increase in synaptosomal [Na+]i and [Ca2+]i (EC50 3 microM), are antinociceptive (ED50, 25 microg/kg), provoke tachyarrhythmia and are highly toxic (LD50 70 microg/kg), whereas low affinity alkaloids reduce [Ca2+]i, induce bradycardia and are less antinociceptive (ED50 20 mg/kg) and less toxic (LD50 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 LD50/ED50 values.

Journal

Title: European Journal of Pharmacology

Abbreviated Title: European Journal of Pharmacology

Publisher: Elsevier BV

ISSN (Print): 00142999

Publication date Created: October 1997

Publication date (Print): October 1997

Volume: 337

Issue: 2-3

Pages: 165-174

Article

DOI: 10.1016/S0014-2999(97)01268-5

PubMed ID: 9430411

SO-VID: 8c09100d-831c-47d5-a72d-31bb9b6a72e1

Copyright statement: © 1997

License:

https://www.elsevier.com/tdm/userlicense/1.0/

Product

Self URI (article page): https://linkinghub.elsevier.com/retrieve/pii/S0014299997012685