succimer and stibocaptate

The currently available anti-leishmanial antimonial drugs, together with other antimony compounds were individually tested, in combination with difluoromethylornithine (DFMO), against experimental murine trypanosomiasis with central nervous system involvement. Satisfactory cure rates could be achieved using a combination treatment of DFMO with most of these anti-leishmanial drugs, but in general, only when they were administered at least twice daily. Of the compounds tested, the most effective was antimony dimercaptosuccinate (Astiban).

Topics: Animals; Antimony; Antimony Sodium Gluconate; Drug Synergism; Drug Therapy, Combination; Eflornithine; Female; Meglumine; Meglumine Antimoniate; Mice; Organometallic Compounds; Succimer; Tartrates; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis, African

Treatment of Schistosoma haematobium (Nigerian strain) in hamsters with a single dose of 40 mg/kg of Astiban caused a reduction in the number of S1, S2, and S3 vitelline cells and an increase in S4 cells. Following seven daily doses of the drug, a marked reduction in S1 cells and a complete loss of S2 and S3 cells occurred such that 95% of the cells were S4 cells, all of which were structurally abnormal. Coagulation and disintegration of the protein granules of the vitelline droplets occurred with increase in lipid droplets, swelling of the nuclear membrane and an increase in cytosegresomes. Blebbing of the tegument in both sexes occurred following a single treatment and vacuolation of the basal infolds and alterations to the mitochondria also resulted, but severe erosion of the tegument was rare even following repeated drug treatment. Damage to the gastrodermis was severe with the development of autophagic vacuoles containing whorls of myelin and sequestered portions of damaged tissue. The degree of damage increased with the number of drug treatments.

Topics: Animals; Cricetinae; Dose-Response Relationship, Drug; Female; Male; Microscopy, Electron; Organometallic Compounds; Schistosoma haematobium; Schistosomiasis haematobia; Schistosomicides; Succimer; Sulfhydryl Compounds

Topics: Adult; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Gluconates; Humans; Injections, Intradermal; Leishmaniasis; Male; Organometallic Compounds; Succimer; Sulfhydryl Compounds

Topics: Adult; Antimony; Antimony Sodium Gluconate; Gluconates; Humans; Leishmaniasis; Male; Organometallic Compounds; Succimer; Sulfhydryl Compounds

Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective against S. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi's equation up to approximately 80% release, with exponentially decreasing release rates thereafter.

Topics: Antimony; Capsules; Humans; Lactates; Lactic Acid; Organometallic Compounds; Polyesters; Polymers; Schistosoma mansoni; Schistosomiasis; Schistosomicides; Succimer; Sulfhydryl Compounds

The effects of Astiban, Lucanthone, Hycanthone and Niridazole on autophagic activities in the gastrodermis of Schistosoma mansoni were determined in vivo, using different dosage levels and dosage times. With Astiban, high levels of autophagy were observed in the gastrodermis 2 hours after an injection of the drug into the mouse, and this response had declined by 20 hours, marking a recovery by the parasite from the drug. Hycanthone and Lucanthone produced an autophagic response several days after the onset of treatment, and no recovery was observed in the morphology of the gastrodermis after the drug was discontinued. The effects of Niridazole on the gastrodermis were to produce the most dramatic ultrastructural changes after high doses and over several days of treatment. With all the drugs examined, gastrodermal autophagy was characterized by the formation of vacuoles containing cell components, lipid droplets and sometimes hydrolytic enzyme reaction product. The autophagic vacuoles appeared to be formed by the sequestration of cytoplasmic material by the basal membrane infoldings, and the transfer of enzymes into the vacuole from within the limiting membrane. The residues from intracellular digestion appeared to be emptied into the caecal lumen.

Topics: Animals; Antimony; Hycanthone; Lucanthone; Mice; Niridazole; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Schistosomicides; Succimer

Topics: Antimony; Antiprotozoal Agents; Drug Evaluation; Female; Humans; Leishmaniasis; Male; Organometallic Compounds; Rifampin; Succimer

Topics: Antimony; Female; Humans; Leishmania; Leishmaniasis; Middle Aged; Organometallic Compounds; Succimer

Topics: Animals; Antimony; Genitalia, Male; Male; Mice; Mice, Inbred Strains; Organometallic Compounds; Schistosoma mansoni; Schistosomicides; Succimer; Sulfhydryl Compounds; Testis

The SbIII preparations available for clinical use were compared in vitro for their concentration/time/effect curves on Trypanosoma venezuelense (T. evansi), measuring decrease of motility and of parasite numbers. With these two criteria leading to similar relative results, the drugs are classified into a rapidly acting group, led by sodium emetic (AST), followed by its dimethylcysteine chelate (NAP) and Anthiomaline, and a less and more slowly acting one: Triostam, Astiban and Stibophen. The relative activity of these drugs in vitro is parallel to that encountered against Schistosoma mansoni, attributed to a similar pattern of intracellular absorption. In vivo effectiveness may depend on bioavailability of Sb in the host and the direct action on the parasite, reflected by its in vitro activity. The interplay of these two factors leads to a different in vitro/in vivo activity relationship of the antimonials even in the same host (mouse) and to its variation in other host species.

Topics: Antimony; Antimony Sodium Gluconate; Benzenesulfonates; Cysteine; In Vitro Techniques; Organometallic Compounds; Succimer; Succinates; Tartrates; Trypanocidal Agents; Trypanosoma

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Succimer; Sulfhydryl Compounds; Time Factors

Topics: Animals; Antimony; Antimony Sodium Gluconate; Benzenesulfonates; Drug Administration Schedule; Mice; Organometallic Compounds; Succimer; Succinates; Time Factors; Trypanosomiasis

Topics: Aged; Antimony; Child, Preschool; Female; Humans; Organometallic Compounds; Schistosomiasis; Succimer; Sulfhydryl Compounds

Topics: Animals; Antimony; Glucuronidase; Kidney; Liver; Mice; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Spleen; Succimer; Sulfhydryl Compounds; Time Factors; Urinary Bladder

Stibocaptate (Asiban, Hoffman--La Roche) killed third stage larvae of Brugia pahangi in vitro at 50 p.p.m. but had no effect on microfilariae at 1 X 10(4) p.p.m No larvae developed in infected mosquitoes fed 1% stibocaptate in 10% sucrose. It was neither micro-nor macrofilaricidal in either jirds or cats but did affect embryogenesis.

Topics: Animals; Antimony; Brugia; Cats; Culicidae; Dose-Response Relationship, Drug; Female; Filarioidea; Male; Organometallic Compounds; Succimer; Succinates

Several drugs were investigated for action against Onchocerca volvulus in chimpanzees. Pentamidine at 4 mg/kg daily for 16 days had no filaricidal action; nor did stibocaptate at 10 mg/kg monthly for 8 months. Hoechst 33258, a substituted bis-benzamidazole, showed micro- and macrofilaricidal activity; F151 (an arsenical compound) showed a purely macrofilaricidal action; and Compound E (a reaction product of Hoechst 33258 and F151) was micro- and macrofilaricidal. The toxicity of the three last-mentioned compounds was high, and further trials were not made. Nifurtimox, at doses of up to 40 mg/kg for 10 days, was shown not be microfilaricidal, but there was a suggestion that this drug may have some macrofilaricidal action.

Topics: Animals; Anthelmintics; Antimony; Arsenicals; Bisbenzimidazole; Female; Male; Nifurtimox; Onchocerca; Onchocerciasis; Organometallic Compounds; Pan troglodytes; Pentamidine; Succimer; Succinates

Topics: Africa; Africa, Western; Antimony; Child; Drug Therapy; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Animals; Anti-Bacterial Agents; Antimony; Intestines; Mice; Organometallic Compounds; Pharmacology; Research; Salmonella; Succimer

Topics: Antimony; Humans; Ions; Organometallic Compounds; Schistosomiasis; Sodium; Sodium, Dietary; Succimer; Succinates; Succinic Acid

Topics: Antimony; Body Fluids; Organometallic Compounds; Polarography; Schistosomiasis; Succimer; Toxicology; Urine

Topics: Animals; Antimony; Autoradiography; Cricetinae; Intestines; Liver; Mice; Organometallic Compounds; Pathology; Radioisotopes; Research; Schistosoma; Schistosoma mansoni; Sodium; Succimer; Succinates; Succinic Acid

Topics: Animals; Antimony; Cricetinae; Dosage Forms; Mice; Organometallic Compounds; Pharmacology; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Adolescent; Antimony; Biomedical Research; Drug Therapy; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer; Toxicology

Topics: Adolescent; Africa; Africa, Western; Antimony; Child; Drug Therapy; Ghana; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Toxicology

Topics: Antimony; Antiprotozoal Agents; Emetine; Mice; Organometallic Compounds; Pharmacology; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Animals; Antimony; Blood; Chemical Phenomena; Chemistry; Cricetinae; Intestines; Kidney; Liver; Mice; Organometallic Compounds; Pharmacology; Radioisotopes; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer

Topics: Animals; Antimony; Antiparasitic Agents; Humans; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Sodium; Succimer

Topics: Acids, Noncarboxylic; Antimony; Humans; Organometallic Compounds; Schistosomiasis; Sodium; Sodium, Dietary; Succimer; Succinates; Toxicology

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Electrocardiography; Organometallic Compounds; Schistosomiasis; Succimer; Succinates; Succinic Acid

Topics: Antimony; Humans; Iraq; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Hepatitis; Hepatitis A; Organometallic Compounds; Schistosomiasis; Shock, Septic; Succimer; Succinates; Succinic Acid

Topics: Antimony; Iraq; Lucanthone; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Heart; Humans; Liver Diseases; Organometallic Compounds; Schistosomiasis; Succimer; Succinates; Sulfhydryl Compounds

Topics: Animals; Antimony; Humans; Organometallic Compounds; Schistosoma haematobium; Schistosomiasis; Schistosomiasis haematobia; Sodium; Sodium, Dietary; Succimer

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Succimer

Topics: Antimony; Antimony Potassium Tartrate; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Somalia; Succimer; Urinary Tract Infections

Topics: Acids, Noncarboxylic; Antimony; Organometallic Compounds; Schistosomiasis; Schistosomiasis japonica; Sodium; Sodium, Dietary; Succimer; Succinates

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Succinates; Urologic Diseases

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Succimer