Alkaloid toxicity indices

CANNABIS CYTOTOXICS -CYCLOPHOSPHAMIDE, DOXORUBICIN, IFOSFAMIDE, LOMUSTINE, VINCA ALKALOIDS Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

Intravenous administration of berberine (20 mg/kg) to anesthetized rats was observed to increase the cardiac index and stroke volume index. In the isolated guinea pig left atria, berberine (0.1 pmol/L) shifted the dose-response curve of ouabain to the left with an increase of the maximal effect. The alkaloid (10 pmol/L and 30 pmol/L) potentiated the maximal contractile force of ouabain and diminished the dose at which ouabain produced its peak effect. Berberine (30 pmol/L and 100 pmol/L) elevated the dose in which the toxicity of ouabain occurred. The investigators concluded that berberine might increase the cardiac output and widen the safety margin with ouabain-treatment [249]. 

This could not be the case of homofascaplysin A (39) [Fig. (11)], a p-carboline-indole alkaloid isolated from the sponge Hyrtios erecta [56], Indeed, homofascaplysin A (39) showed activity against chloroquine-resistant P. falciparum strains with an IC50 of about 20 ng/mL, but its toxicity toward rat skeletal muscle myoblast cells was estimated to be less than 1 pg/mL, and thus the selectivity index of this molecule is very narrow. 

These alkaloids were not toxic to S. littoralis, while aconitine negatively affected both feeding indexes (RCR and RGR, table 15). Their toxicity on L. decemlineata was inversely correlated with their antifeedant effects, the amino alcohol (31) derivative being the most toxic (table 15). None of the test compounds proved to be as toxic as aconitine on this insect species [20]. 

Pasqual, M.S., C.P. Lauer, P. Moyna, and J.A.P. Henriques. 1993. Genotoxicity of the isoquinoBne alkaloid berberine in prokaryotic and eukaryotic organisms. Mutat. Res. 286(2) 243-252. Price, C.J., and J.D. George. 2003. Final study report on the developmental toxicity evaluation for berberine chloride dihydrate (CAS No. 5956-60-5) administered in the feed to Swiss (CD-1 ) mice on gestational days 6 through 17. Gov. Rep. Announce. Index No. 20 112. 

Experiments with animals have revealed that ajmaline (L, Fig. 4) has promising quinidine-like anti-arrhythmic properties and an apparently favourable therapeutic index [1105-1120], but neither the alkaloid itself nor any of its less toxic semi-synthetic derivatives [1121-1129] has gained a firm place in clinical medicine, although ajmaline has seen occasional application in the control of extrasystoles [1130, 1131]. 

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