Pentavalent Antimony Compounds Research Articles

Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies.

Pentavalent antimonial compounds have been the mainstay of the treatment of visceral, cutaneous, and mucosal leishmaniasis for approximately half a century. Pentostam (sodium stibogluconate) is the pentavalent antimonial compound available in the United States (through the Centers for Disease Control). As dosage regimens for treating leishmaniasis have evolved, the daily dose of antimony and the duration of therapy have been progressively increased to combat unresponsiveness to therapy. In the 1980s, the use of 20 mg/kg/day (instead of 10 mg/kg/day) of antimony was recommended, but only to a maximum daily dose of 850 mg. The authors have concluded on the basis of recent efficacy and toxicity data that this 850-mg restriction should be removed; the evidence to date, which is summarized here, suggests that a regimen of 20 mg/kg/day of pentavalent antimony, without an upper limit on the daily dose, is more efficacious and is not substantially more toxic than regimens with lower daily doses. We recommend treating all forms of leishmaniasis with a full 20 mg/kg/day of pentavalent antimony. We treat cutaneous leishmaniasis for 20 days and visceral and mucosal leishmaniasis for 28 days. Our judgment of cure is based on clinical criteria.

Activité antiparasitaire d'alcaloïdes bisbenzylisoquinoleiques. I: activité in vitro sur des promastigotes de trois souches de Leishmania

Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The Chemotherapic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous lieshmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).

Evidence for a membrane adenosine receptor in Leishmania mexicana mexicana (WR 227).

Leishmania spp., a Protozoan Parasite transmitted to the mammalian host by the sand fly (genus Phlebotomus), produces a disease manifested in the cutaneous, mucocutaneous or visceral form. The choice of drugs has been limited primarily to the pentavalent antimonial compounds. Successful treatment within the endemic tropical areas of the world varies due to problems of drug resistance and to strain differences in Leishmania Spp. These difficulties have prompted the search for new effective oral antileishmanial agents and ultimately the development of a vaccine. We are currently studying proteins on the parasite plasma membrane (enzymes, receptors, transporters) which may be functionally vital to the organism and amenable to chemotherapeutic attack or elicit a host immune response. The present study examines evidence for an adenosine receptor on the surface membrane of both the promastigote (insect stage) and the amastigote form (mammalian stage) and the resultant modu-lation of adenylate cyclase activity, intracellular cyclic AMP levels, i the rate of cell growth and parasite transformation.

American Cutaneous Leishmaniasis

American leishmaniasis, a disease limited to the American tropics and relatively unfamiliar to North American physicians, is seen in the United States with increasing frequency since the advent of air travel. In contrast to a recent report of successful treatment with metronidazole, our experience of failure in five of six cases indicates that this drug is ineffective. UnlikeLeishmania tropica, which causes the Old World form of cutaneous leishmaniasis,L braziliensiscan persist after disappearance of the primary ulcer and subsequently produce severely mutilating mucosal lesions. Because of this danger, complete eradication of the parasite is extremely important and, in spite of recognized disadvantages, pentavalent antimonial compounds remain the drugs of choice for this infection. (JAMA228:1256-1258, 1974)

American cutaneous leishmaniasis. Inefficacy of metronidazole in treatment.

American leishmaniasis, a disease limited to the American tropics and relatively unfamiliar to North American physicians, is seen in the United States with increasing frequency since the advent of air travel. In contrast to a recent report of successful treatment with metronidazole, our experience of failure in five of six cases indicates that this drug is ineffective. UnlikeLeishmania tropica, which causes the Old World form of cutaneous leishmaniasis,L braziliensiscan persist after disappearance of the primary ulcer and subsequently produce severely mutilating mucosal lesions. Because of this danger, complete eradication of the parasite is extremely important and, in spite of recognized disadvantages, pentavalent antimonial compounds remain the drugs of choice for this infection. (JAMA228:1256-1258, 1974)

Leishmaniasis in the United States

We treated ten cases of leishmaniasis caused by Leishmania braziliensis . The patients had been in an endemic area for ten days as part of a military exercise. The cutaneous lesions were chronic and unresponsive to antibiotic therapy. Treatment consisted of daily intramuscular injections of sodium stibogluconate, a pentavalent antimony compound, and serious side effects were not encountered. The diagnosis of leishmaniasis is usually easily made and should be considered in patients who have recently returned from endemic areas.

Thermal decomposition of alkoxy and aroxy derivatives of pentavalent phosphorus and antimony compounds

The thermal decomposition of Ph 4POPh and Ph 4SbOR [R = CH 3; (CH 3) 2-CH; Ph] has been investigated. The decomposition of tetraphenylphenoxyphosphorane gives triphenylphosphine, phenol and other products resulting from the condensation of the intermediate dehydrobenzene. Alkoxy derivatives of tetraphenylantimony decompose to give triphenylstibine, aldehyde or ketone and benzene. The reaction is accompanied by the formation of simple ethers which is a basic characteristic of the behavior of tetraphenylphenoxyantimony.

Treatment of Kala-azar: Past, Present & Future

More than 90 percent of cases of kala-azar in the world occur in India, Bangladesh, Nepal, Sudan, and Brazil. Nearly 25 compounds are reported to have anti-leishmanial effects but not all are in use. The pentavalent antimony compounds have remained as mainstay of treatment for nearly 75 years. However, emergence of resistance led to the use of other compounds like amphotericin B, pentamidine, paromomycin, miltefosine etc. Miltefosine is the only oral agent available and recently has been recommended in the National guideline of Bangladesh. But it has a long half-life of 154 hour and this could encourage development of clinical resistance. Further, rapid therapeutic response along with unsupervised treatment can severely affect compliance, and bring a premature end to this very important arsenal against leishmania. Stimaquine is other oral agent coming in near future along with some promising immunotherapeutic agents and of course the possibility of a vaccine. We can assume that in future, combination of drug will be the desirable solution to combat Kala-azar. Â DOI = 10.3329/jom.v9i2.1438 J MEDICINE 2008; 9 : 90-95

Synthesis of RAr2SbCl2 and Ar'Ar2SbCl2 by exchange of Ar2SbCl2 with HgR2 OR HgAr2

1. A method has been proposed for the synthesis of pentavalent antimony compounds containing three identical or different groups by use of fully substituted mercury compounds. 2. The cis and trans isomers ofβ-chlorovinyldiphenylantimony dichloride have been prepared, and their structure has been established on the basis of their NMR and IR spectra.

The stereochemistry of pentavalent antimony compounds

A survey of the crystal chemistry of simple and complex pentavalent antimony compounds is presented. It follows from the analysis of structural data that "closed" polyhedra with coordination numbers 4, 5, and 6 without additional bonds of antimony with farther removed atoms are, as a rule, formed around the pentavalent antimony atom. The coordination number four with a tetrahedral configuration is extremely rarely encountered. The coordination number five with the configuration of a trigonal bipyramid is characteristic for simple halides and also for organometallic compounds of pentavalent antimony. The coordination number six (octahedral form) is found in complex halides, halides with additional donor ligands, and likewise in all oxygen compounds. The interatomic Sb-ligand distances in the trigonal bipyramid are non-equivalent: the bonds to the three ligands located in the equatorial plane of the molecule are more stable than those to the two "peaks." The Sb-halogen distances in octahedral complexes may vary over a wide range even when the "bridge" atoms are excluded from consideration. The scattering of interatomic Sb-O distances in the oxygen compounds, is, as a rule, small.

The infrared spectra of some phenyl-substituted pentavalent antimony compounds

In compounds of the type Ph 3SbY 2 and (Ph 3Sb-O-SbPh 3Y 2 the C(Ph)-Sb asymmetric stretching frequency occurs between 471 and 445 cm -2. Absorption due to Sb-O-Sb occurs near 750 cm -2. In triphenylantimony dinitrate the nitrate group is considerably more covalent than in trimethylantimony dinitrate. The spectral results with compounds of the type Ph 3SbY 2 are consistent with a trigonal bipyramidal molecule. X-ray diffraction studies by previous workers have clearly demonstrated such a structure for only Ph 3SbCl 2. Oxybis(triphenylantimony) diperchlorate appears to contain a perchlorate ion. The other compounds of the type (Ph 3Sb-O-SbPh 3)Y 2 which we have studied appear to be covalent and probably consist of two trigonal bipyramidal Ph 3SbY groups sharing an apical oxygen atom.

The Infrared Spectra of Some Alkyl-Substituted Pentavalent Antimony Compounds

The Infrared Spectra of Some Alkyl-Substituted Pentavalent Antimony Compounds

Detoxication of a Substituted Phenyl Stibonate in the Rat by Administration of p-Aminobenzoic Acid

The writer has reported1 experiments that demonstrated the highly protective powers of p-aminobenzoic acid when administered in substantial but well tolerated quantities to rats that simultaneously had received high lethal doses of Carbarsone, “Tryparsamide,” arsan-ilic acid, and Acetarsone. Further experiments, to be published in extenso elsewhere, have shown that p-aminobenzoic acid provides equally high protection against other penta-valent arsenicals including phenyl arsonic acid and also against at least one of the trivalent arsenical antisyphilis drugs.In view of the therapeutic value placed upon some of the less toxic antimony compounds in the treatment of such important tropical diseases as kala-azar and schistosomiasis, it seems desirable to record the capacity of p-aminobenzoic acid to protect rats against acute fatal doses of the German proprietary drug, “Stibosan” (sodium m-chloro p-acetyl amino phenyl stibonate), the only pentavalent antimony compound which was presently available for test pu...

USE OF A PENTAVALENT ANTIMONY COMPOUND FOR TREATING KALA-AZAR IN CHILDREN

This report is concerned with presenting in detail the routine administration of a pentavalent antimony compound¹for treating a child with kala-azar, and with reviewing the therapeutic value of this drug in treating kala-azar in children of North China. <h3>REPORT OF A CASE</h3> M. W. Ch'en, a Chinese boy aged 9 years, came from a village in a region where kala-azar was endemic. He had been healthy until fifteen months before admission, when his father noticed that the child was gradually becoming listless. For nine months before admission he had frequent irregular attacks of fever. Since the onset of the present illness there had been gradual loss of appetite, strength and weight and frequent attacks of bleeding from the nose and gums. A mass reaching 2 fingerbreadths below the left costal margin was noticed in the upper part of the abdomen eight months before admission. This mass had gradually