U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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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.
Status:
Possibly Marketed Outside US
Source:
Uzara by Tschesche, R.|Brathge, K.H.
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Conditions:

Uzarigenin is a Na(+), K(+)-ATPase inhibitor; potential anticancer drug. Uzarigenin is a component of Uzara, which has been used for a long time in traditional medicine to treat diarrheal disorders, but the mode of action is not fully known. In Germany, Uzara (Stada, Bad Vilbel, Germany) is frequently used as over-the-counter preparation of the Uzara root, containing 40 mg glycosides/ml.
Ivermectin is a broad-spectrum anti-parasite medication. It was first marketed under the name Stromectol® and used against worms (except tapeworms), but, in 2012, it was approved for the topical treatment of head lice infestations in patients 6 months of age and older, and marketed under the name Sklice™ as well. Ivermectin is mainly used in humans in the treatment of onchocerciasis but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis, and enterobiasis). Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair the normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It is sold under brand names Heartgard, Sklice and Stromectol in the United States, Ivomec worldwide by Merial Animal Health, Mectizan in Canada by Merck, Iver-DT in Nepal by Alive Pharmaceutical and Ivexterm in Mexico by Valeant Pharmaceuticals International. In Southeast Asian countries, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6.