Repurposing antipsychotic and sleep disorder drugs as anti-parasitics
Antipsychotic and sleep disorder drugs represent a rapidly growing, global market (1). Novel drugs targeting melatonin (2), serotonin (3), dopamine (4), and GABA (5) receptors are being developed. Historically, related compounds have been identified as demonstrating activity against flatworms and the model nematode Caenorhabditis elegans, but nothing has been done to reconcile the recent growing diversity of chemical derivatives with potential activity against parasitic worms (6).
Melatonin is a well-known regulator of circadian rhythms in mammals, and Prazosin, an agonist of the mammalian melatonin 3 receptor, triggers various defects in C. elegans (7). Melatonin has also been shown to promote protective effects in mice infected with Schistosoma mansoni (8).
Ivermectin is a potent anti-parasitic which agonizes GABA receptors, causing flaccid paralysis and parasite death. Benzodiazepine and non-benzodiazepine GABA receptor agonists could therefore prove effective anthelmintics. Ivermectin exposure has also been found to enhance binding of certain benzodiazepine-derivatives in rats (9) providing some rationale for exploring combinatorial therapies. Benzodiazepine derivatives have historically proven effective as anti-schistosomals (10), providing further evidence of anti-parasitic efficacy within the family.