Anthelmintic + antiprotozoal targets
Category: catabolism
Overview
Parasites split into helminths (worms — nematodes, cestodes, trematodes) + protozoa (single-celled — Plasmodium, Trichomonas, Giardia, Entamoeba). Anthelmintic mechanisms exploit parasite-specific biology: ivermectin opens glutamate-gated chloride channels (insect/nematode-specific) → paralysis (avermectin class); benzimidazoles (albendazole, mebendazole) bind parasite β-tubulin selectively (low mammalian affinity) → microtubule disruption; praziquantel disrupts cestode/trematode tegument calcium homeostasis; pyrantel (covered as pk_unauthored local-acting) depolarizes neuromuscular junction. Antiprotozoals: artemisinin generates parasite-specific peroxide radicals in heme-rich Plasmodium digestive vacuole; hydroxychloroquine concentrates in the same acidic vacuole → heme polymerization block; quinine — historical cinchona alkaloid still used for chloroquine-resistant malaria; nitazoxanide blocks pyruvate-ferredoxin oxidoreductase (PFOR, anaerobe-specific).
Organ Systems
- digestive
- immune-hematologic
Pathway Steps
- parasite-targets → parasite-clearance — via mechanism varies — ion channels, tubulin, mitochondrial function, heme polymerization. Antiparasitic drugs exploit parasite-specific targets: ivermectin opens invertebrate glutamate-gated chloride channels (paralysis), benzimidazoles bind parasite β-tubulin, and praziquantel disrupts schistosome calcium homeostasis. The diversity of helminth and protozoan biology is why antiparasitic therapy is so organism-specific.
Known Modulators
- ivermectin (activator) — glutamate-gated Cl⁻ channels (invertebrate-specific). macrocyclic lactone; onchocerciasis + strongyloides + scabies; mammalian GABA-A receptors are inaccessible due to BBB P-gp (mammalian safety margin)
- albendazole (inhibitor) — parasite β-tubulin. benzimidazole; broad anthelmintic; sulfoxide metabolite is the active species
- mebendazole (inhibitor) — parasite β-tubulin. benzimidazole; pinworm/whipworm/ascaris; minimal systemic absorption (~5%) — gut-active
- praziquantel (activator) — parasite Ca²⁺ channels (tegument). schistosomiasis + cestodes; massive Ca²⁺ influx → tegument disruption + paralysis
- pyrantel pamoate (activator) — parasite nAChR (depolarizing block). pinworm/roundworm; pk_unauthored local-acting (pamoate-engineered for gut retention)
- nitazoxanide (inhibitor) — pyruvate-ferredoxin oxidoreductase (PFOR). Cryptosporidium + Giardia; anaerobe-specific energy disruption
- artemisinin (activator) — heme-Fe radical generation (peroxide bridge). P. falciparum; ACT (artemisinin combination therapy) gold standard for uncomplicated malaria; short t½ → combination prevents resistance
- hydroxychloroquine (inhibitor) — heme polymerization (parasite digestive vacuole). malaria + lupus + RA; retinopathy at chronic dose (~5 mg/kg/d limit + screening); QT prolongation
- quinine (inhibitor) — heme polymerization. cinchona alkaloid; severe malaria; cinchonism (tinnitus + headache); hyperinsulinemia + hypoglycemia tail; CYP2D6 potent inhibitor
References