Helminth nicotinic acetylcholine receptor (nAChR) (nAChR)

Helminth nicotinic acetylcholine receptors (nAChRs) are essential pentameric ligand-gated ion channels that mediate rapid excitatory neurotransmission in parasitic worms (Martin et al., 2012, PMID: 22414772). These receptors are located primarily at neuromuscular junctions, where they regulate muscle contraction and locomotion by allowing the influx of cations like sodium and calcium upon activation by acetylcholine (Putrenko et al., 2005, PMID: 15831499). They are a major target for anthelmintic therapy, with drugs such as levamisole and pyrantel acting as agonists that induce spastic paralysis in the parasite (Abongwa et al., 2017, PMID: 28634334). Newer drug classes, such as the amino-acetonitrile derivatives (e.g., monepantel), target specific nematode-only nAChR subunits like ACR-23, providing high selectivity and efficacy against parasites resistant to older treatments (Kaminsky et al., 2008, PMID: 18235498). The structural and pharmacological diversity of these receptors across different helminth species makes them a versatile yet challenging target for drug development, especially given the rising global threat of anthelmintic resistance (Wolstenholme, 2011, PMID: 21612600).

Other names

Nematode nicotinic acetylcholine receptorParasitic worm nAChRLevamisole-sensitive receptorMonepantel-sensitive receptorCys-loop ligand-gated ion channelACR-23 receptorUNC-38/UNC-29 complex

Agonists cause persistent depolarization of muscle cells leading to spastic paralysis; antagonists cause flaccid paralysis (Martin et al., 2012, PMID: 22414772).