Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus.
Level 5 - mechanism / opinion, no new human data
Bench/in vitro biochemical research (CEBM Level 5).
PubMed 2325707 · doi:10.1016/0166-6851(90)90025-h
What was done
Researchers evaluated the specific high-affinity binding of tritiated benzimidazoles ([3H]mebendazole and [3H]oxibendazole) and displacement by unlabelled benzimidazoles (oxibendazole, mebendazole, oxfendazole, albendazole, fenbendazole, thiabendazole) using crude tubulin extracts from thiabendazole-susceptible and thiabendazole-resistant strains of adult *Haemonchus contortus*.
What was found
The abstract reports no numerical values. Drug binding at infinite ligand concentration (Bmax) was markedly reduced in the resistant strain relative to the susceptible strain, with no apparent change in association constant (Ka). Low-affinity binding was unaltered. The loss of high-affinity binding sites was greater for [3H]oxibendazole than for [3H]mebendazole. Benzimidazole rank order by Ka and IC50 was approximately independent of radioligand displaced or tubulin strain source.
Why it matters
This study provides biochemical evidence that benzimidazole anthelmintic resistance stems from a loss of high-affinity tubulin binding sites rather than altered affinity, confirming tubulin interaction as the common primary mechanism of action across benzimidazoles.
Limits
The study is an in vitro assay on crude parasite tubulin extracts rather than whole in vivo models. The abstract does not provide exact numerical values, confidence intervals, or sample/replicate sizes.
Cited by
- contradicts Mebendazole exerts its anti-parasitic and anti-cancer effects by targeting the glutaminolysis pathway.