Paraherquamide (PHQ), a potent and broad-spectrum anthelminthic. Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs of these compounds rapidly induce flaccid paralysis in parasitic nematodes in vitro, without affecting adenosine triphosphate (ATP) levels. Paraherquamide anthelmintics are nicotinic cholinergic antagonists in both nematodes and mammals, and this mechanism appears to underlie both their efficacy and toxicity. Paraherquamide A is a natural product produced by Penicillium paraherquei which was discovered in 1981. It was evaluated by Merck in the late 1980’s and a small chemistry effort was conducted to produce analogs. Paraherquamide A was found to have outstanding broad spectrum nematocidal activity against various sheep gastro-intestinal nematodes. It is a nicotinic antagonist that blocks depolarization in muscles and induces a rapid paralysis of the mid-body of the parasite. However, it was severely toxic in mice and dogs, which prevented its development, as these species are the standard models for safety studies.