Studies of the Mode of Action of Metrifonate and DDVP in Schistosomes ‐ Cholinesterase Activity and the Hepatic Shift

Bloom, A

doi:10.1111/j.1600-0773.1981.tb03260.x

Cited by 15 publications

(2 citation statements)

References 20 publications

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“…Contrawise, it can be assumed that the pharmacologically damaged worms could become sequestered and killed by physical factors or nutritional deficiencies or − which is the most likely event − by cell-mediated mechanisms of cytotoxicity as high numbers of immunocompetent cells such as eosinophils and alveolar macrophages are present in the lungs. Experimental evidence supports this hypothesis [66]. Based on its pharmacological characteristics fears about toxicity of metrifonate persisted for some time.…”

Section: Pharmacology and Toxicologymentioning

confidence: 87%

Therapeutic and Operational Profiles of Metrifonate and Praziquantel in Schistosoma haematobium Infection

Feldmeier

Chitsulo

2011

Arzneimittelforschung

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A systematic analysis of the existing literature has been undertaken to compare the therapeutic and operational profiles of metrifonate (CAS 52-68-6), and praziquantel (CAS 55-268-74-1), two anti-schistosomal compounds. The criteria evaluated were therapeutic efficacy against Schistosoma haematobium and other helminths, impact on pathology commonly associated with S. haematobium infection, frequency, type and duration of adverse reactions, health risk associated with inadvertent overdosage, applicability and practicality of treatment in various medical settings, tolerance and resistance, pharmacological properties, toxicity and economic aspects. It is concluded that both medical and operational criteria indicate that praziquantel is superior to metrifonate for the treatment of schistosomiasis caused by S. haematobium. Since, compared to praziquantel, metrifonate has a number of disadvantages, future antischistosomal chemotherapy can do without this drug.

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Section: Pharmacology and Toxicologymentioning

confidence: 87%

Therapeutic and Operational Profiles of Metrifonate and Praziquantel in Schistosoma haematobium Infection

Feldmeier

Chitsulo

2011

Arzneimittelforschung

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“…The increasing reliance, therefore, on a single partially effective drug highlights the importance of discovering new anti-schistosomal chemistries. In parasitic helminths (nematodes and flatworms), the nervous system has been a rich source of drug targets ( Robertson and Martin, 2007 ; Kaminsky et al, 2008 ; Gutman et al, 2010 ; Wolstenholme, 2011 ) with many anthelmintics acting on proteins involved in neuronal signaling to induce spastic or flaccid paralysis ( Bueding et al, 1972 ; Bloom, 1981 ; Geerts et al, 1989 ; Gill et al, 1991 ; Geary et al, 1993 ; Caffrey et al, 2012 ), and subsequent elimination of the parasite from the host.…”

Section: Introductionmentioning

confidence: 99%

Octopamine signaling in the metazoan pathogen S chistosoma mansoni: localization, small-molecule screening and opportunities for drug development

El-Sakkary

Chen

Arkin

et al. 2018

Disease Models &Amp; Mechanisms

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Schistosomiasis is a tropical disease caused by a flatworm trematode parasite that infects over 200 million people worldwide. Treatment and control of the disease rely on just one drug, praziquantel. The possibility of drug resistance coupled with praziquantel's variable efficacy encourages the identification of new drugs and drug targets. Disruption of neuromuscular homeostasis in parasitic worms is a validated strategy for drug development. In schistosomes, however, much remains to be understood about the organization of the nervous system, its component neurotransmitters and potential for drug discovery. Using synapsin as a neuronal marker, we map the central and peripheral nervous systems in the Schistosoma mansoni adult and schistosomulum (post-infective larva). We discover the widespread presence of octopamine (OA), a tyrosine-derived and invertebrate-specific neurotransmitter involved in neuromuscular coordination. OA labeling facilitated the discovery of two pairs of ganglia in the brain of the adult schistosome, rather than the one pair thus far reported for this and other trematodes. In quantitative phenotypic assays, OA and the structurally related tyrosine-derived phenolamine and catecholamine neurotransmitters differentially modulated schistosomulum motility and length. Similarly, from a screen of 28 drug agonists and antagonists of tyrosine-derivative signaling, certain drugs that act on OA and dopamine receptors induced robust and sometimes complex concentration-dependent effects on schistosome motility and length; in some cases, these effects occurred at concentrations achievable in vivo. The present data advance our knowledge of the organization of the nervous system in this globally important pathogen and identify a number of drugs that interfere with tyrosine-derivative signaling, one or more of which might provide the basis for a new chemotherapeutic approach to treat schistosomiasis..

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Antiparasitic Agents, Anthelmintics

Becher¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Human infections caused by worms (helminths) represent one of the most important public health problems in the world. Helminths form three main categories or phyla: Platyhelminths, flatworms; Aschelminthes, roundworms; and Nemathelminthes, thorny‐headed worms. Substantial progress in the discovery and development of anthelmintic drugs has been made. Effective agents are available for most human gastrointestinal infections; however, drugs that are effective in treating the extraintestinal complications of many helminthic infections are still needed. Agents include praziquantel for the treatment of flukes, eg, C. sinensis ; tapeworms, eg, H. nana ; and larval stage (cysticercosis); oxamniquine for the treatment of flukes ( S. mansoni ); metrifonate for the treatment of blood flukes ( Schistosoma haematobium ); bithionol for the treatment of lung flukes ( Paragonimu westermani ), sheep liver flukes ( Fasciola hepatica ); tetrachloroethylene for the treatment of intestinal fluke ( Fasicolopsis buski ); niclosamide for the treatment of tapeworms ( T. saginata, T. solium , and D. latum ); quinacrine for the treatment of pork tapeworm ( Taenia solium ); piperazine citrate for the treatment of roundworms ( Ascaris lumbricoides ); diethylcarbamazine citrate for the treatment of lymphatic filariases ( Wuchereria bancrofti, Loa loa , and other filaria); pyrantel pamoate for the treatment of pinworms ( Enterobius vermiculus ), roundworms ( Ascaris lumbricoides ), hookworms ( Ancyclostoma duodenale, Necator americanus ); mebendazole for the treatment of (whipworms ( Trichuris trichiura ), hookworms ( Ancylostoma duodenale, Nector americanus ), filariasis ( Mansonella perstans ), roundworm ( Ascaris lumbricoides ), Trichinosis ( Trichinella spiralis ); thiabendazole for the treatment of hookworms ( Trichostrongylus sp., cutaneous larva migrans, Angiostrongylus costaricensis , and Strongyloides stercoralis ); and ivermectin for the treatment of filariasis ( Onchocerca volvulus ). Frequently, the treatment of helminthic diseases requires adjunct medication eg, antihistamines and corticosteroids. Allergic reactions are commonly seen as a result of tissue invasion by worms or as a consequence of anthelmintic therapy. Three main species of blood flukes cause schistosomiasis in humans: Schistosoma haematobium, S. mansoni , and S. japonicum . The effectiveness of antischistosomal drugs depends on the reduction or arrest of egg production. Infection only occurs as a result of the penetration of the intact skin by free‐swimming cercaria. After they develop to preadult forms in the skin and lung, the parasites migrate through host blood vessels to various tissues. Adult worms that are approximately 2 cm in length remain paired within the portal or intestinal vasculature of the host. The female, however, travels as far as possible toward the capillary beds to lay eggs, a portion of which embolize to the liver and induce granuloma formation. During the early stages of the disease, patients may experience fever, gastrointestinal distress, headache, and fatigue. In later stages of the disease, signs of hepatic fibrosis and ascites are seen. The number of worm pairs found in a patient may vary from a few to over 100. In untreated patients, adult worms are now generally assumed to live less than 5–10 years. Praziquantel , C 19 H 24 N 2 O 2 , can be used to treat schistosomiasis caused by any one of the three major species. Praziquantel is an acylated pyrazino–isoquinoline derivative that has replaced the traditional (and more toxic) trivalent antimonial compounds.

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Studies of the Mode of Action of Metrifonate and DDVP in Schistosomes ‐ Cholinesterase Activity and the Hepatic Shift

Cited by 15 publications

References 20 publications

Therapeutic and Operational Profiles of Metrifonate and Praziquantel in Schistosoma haematobium Infection

Therapeutic and Operational Profiles of Metrifonate and Praziquantel in Schistosoma haematobium Infection

Octopamine signaling in the metazoan pathogen S chistosoma mansoni: localization, small-molecule screening and opportunities for drug development

Antiparasitic Agents, Anthelmintics

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