Novos esquistossomicidas

Argento, Carlos A.; Neves, Paulo F.; Galvão, Fernando A.; Penna, Delvaux R.; Silva, J. Rodrigues da

doi:10.1590/S0037-86821967000200003

Resumos

Os autores apresentam sua experiência com três novos esquistossomicidas - Ciba 32 644-Ba, Hycanthone e A 16 612, um derivado da piperazina, tecendo considerações sobre sua eficácia e tolerabilidade.

I. The authors describe the preliminary results of therapeutical trials carried out with CIBA 32 644-Ba (1-(5-nitro-2thiazolil) 2-imidazolidinone), a new compound, which has been shown effective in animal experiments against Schistosoma haematobium and Schistosoma mansoni. 221 patients found to be infected with Schistosoma mansoni (rectal biopsy and stool sedimentation) were submitted to the trials. From these, only 21 had splenomegaly while the 200 others were cases of the intestinal or intestino-hepatic form of the disease. Four different schedules were used: A) Constituted of 30 patients who were given 20-25 mg/kg/daily for 10 days; B) constituted of 40 patients who received 30-40 mg/kg/daily for 7 days; C) constituted of 15 patients who were given 30-40 mg/kg/daily for 10 days; D) constituted of 106 patients who were given 30-40 mg/kg/daily for 5 days. The tolerance to the drug was considered rather satisfactory, in spite of some side-effects (headache, nausea, anorexia, abdominal pain, vomiting and dizziness), which ocurred in 40-78% of the cases. In 15 cases ocurred mental symptoms and or convulsion, represented by hallucination and mental excitement. Even so, only in one case these side-effects were more conspicuous so as to require specialized treatment. Liver function tests, blood cells studies and urinalysis were carried out in most of the patients, before and after treatment and showed no significant ehanges. Spermatograms, carried out in some patients, before and after treatment, showed changes (decrease in number and in motility) in about half of the cases, but these returned to normal, later on. Needle biopsy of the liver failed to demonstrate evidence of hepatic damage in all six cases submitted to that study. The effect of therapy on the clinical picture cannot yet lead to conclusions, because of the difficulties in the observations regarding this angle, but the parasitological observations revealed that CIBA 32 644-Ba was more than 90% effective at least in suppressing oviposition, since all the patients submitted to follow-up between 80 and 180 days, in 131 patients, through stool examination (every 1 or 2 months) and at least one rectal biopsy, failed to eliminate viable Schistosoma eggs, during the period of observation. Only in a very small number of cases, rectal biopsy studies still showed dead eggs - a fact which deserves further investigation. II - HYCANTHONE - It was given to 17 patients with froom tolerance in higher doses (5 mg/kg/daily during 5 days) and acceptable tolerance with 3 mg/kg/daily during 5 days. Only 7 patients who completed treatment were submitted to control of cure for 40-120 days following treatment. 2 out of the seven patients continued to pass eggs 40-50 days after treatment. III - A-16 612, a piperazine compound, was given to 32 patients. Tolerance was poor with higher doses, which, even so, were not curative.

Novos esquistossomicidas

Carlos A. Argento^I; Paulo F. Neves^II; Fernando A. Galvão^II; Delvaux R. Penna^III; J. Rodrigues da Silva^IV

^IAssistente da Cadeira de Clínica de Doenças Tropicais e Infectuosas da F.M. da U.F.R.J.

^IIAssistentes da Cadeira de Clínica de Doenças Infectuosas e Parasitárias da F.C.M. da U.E.G.

^IIIBolsista do I.N.E.Ru.

^IVProfessor Catedrático da Cadeira de Clínica de Doenças Tropicais e Infectuosas da F.M. da U.F.R.J. e interino da F.C.M. da U.E.G. Diretor do Instituto Nacional de Endemias Rurais (DNERu, M.S.)

RESUMO

Os autores apresentam sua experiência com três novos esquistossomicidas - Ciba 32 644-Ba, Hycanthone e A 16 612, um derivado da piperazina, tecendo considerações sobre sua eficácia e tolerabilidade.

ABSTRACT

I. The authors describe the preliminary results of therapeutical trials carried out with CIBA 32 644-Ba (1-(5-nitro-2thiazolil) 2-imidazolidinone), a new compound, which has been shown effective in animal experiments against Schistosoma haematobium and Schistosoma mansoni.

221 patients found to be infected with Schistosoma mansoni (rectal biopsy and stool sedimentation) were submitted to the trials. From these, only 21 had splenomegaly while the 200 others were cases of the intestinal or intestino-hepatic form of the disease. Four different schedules were used: A) Constituted of 30 patients who were given 20-25 mg/kg/daily for 10 days; B) constituted of 40 patients who received 30-40 mg/kg/daily for 7 days; C) constituted of 15 patients who were given 30-40 mg/kg/daily for 10 days; D) constituted of 106 patients who were given 30-40 mg/kg/daily for 5 days.

The tolerance to the drug was considered rather satisfactory, in spite of some side-effects (headache, nausea, anorexia, abdominal pain, vomiting and dizziness), which ocurred in 40-78% of the cases. In 15 cases ocurred mental symptoms and or convulsion, represented by hallucination and mental excitement. Even so, only in one case these side-effects were more conspicuous so as to require specialized treatment.

Liver function tests, blood cells studies and urinalysis were carried out in most of the patients, before and after treatment and showed no significant ehanges. Spermatograms, carried out in some patients, before and after treatment, showed changes (decrease in number and in motility) in about half of the cases, but these returned to normal, later on. Needle biopsy of the liver failed to demonstrate evidence of hepatic damage in all six cases submitted to that study.

The effect of therapy on the clinical picture cannot yet lead to conclusions, because of the difficulties in the observations regarding this angle, but the parasitological observations revealed that CIBA 32 644-Ba was more than 90% effective at least in suppressing oviposition, since all the patients submitted to follow-up between 80 and 180 days, in 131 patients, through stool examination (every 1 or 2 months) and at least one rectal biopsy, failed to eliminate viable Schistosoma eggs, during the period of observation. Only in a very small number of cases, rectal biopsy studies still showed dead eggs - a fact which deserves further investigation.

II - HYCANTHONE - It was given to 17 patients with froom tolerance in higher doses (5 mg/kg/daily during 5 days) and acceptable tolerance with 3 mg/kg/daily during 5 days. Only 7 patients who completed treatment were submitted to control of cure for 40-120 days following treatment. 2 out of the seven patients continued to pass eggs 40-50 days after treatment.

III - A-16 612, a piperazine compound, was given to 32 patients. Tolerance was poor with higher doses, which, even so, were not curative.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

BIBLIOGRAFIA

Trabalho da Cadeira de Clínica de Doenças Tropicais e Infectuosas da Faculdade de Medicina da Universidade Federal do Rio de Janeiro e da Cadeira de Clínica de Doenças Infectuosas e Parasitárias da Faculdade de Ciências Médicas da Universidade do Estado da Guanabara, sob o patrocínio e a colaboração do Instituto Nacional de Endemias Rurais (DNERu, Ministério da Saúde) e ainda, parcialmente com a ajuda do Grant AI-0518803 do U.S.P.H.S. (National Institutes of Health).

Referências bibliográficas

1. ARGENTO, C.A.; NEVES, P.F.; GALVAO, F. A. & RODRIGUES DA SILVA, J. - O composto CIBA 32 644-Ba (Aminonitrotiazol) no tratamento da Esquitossomose mansoni. Fôlha Médica. Rio, 5:7, 1965.
2. BARANSKI, M .C. - Comunicação pessoal, 1966.
3. BARANSKI, M.C. & SILVA, A.F. - Ineficácia do tratamento da esquistossomose mansônica pelo A 16 612 (n(3- cloro-4-metilfenil) - n'(4-t'-amilfenoxi-hexametileno) cloridrato de piperazina. Trabalho apresentado ao XVI Cong. Bras. de Hig., Curitiba, 1966.
4. BUEDING, E. & SCHILLER, E. - Mechanism of action of antischistosomal drugs. Abstracts of the International Pharmacological Congress, São Paulo, soai, 1966.
5. CARVALHO NETO, Comunicação pessoal, 1966.
6. COUTINHO, A.; LIMA, C.A. & ALVES C. - A clinical trial of CIBA 32 644- Ba. Therapeutique Nouvelle de la bilharziose et de l'amebiase. Acta Tropica, supplementum 9: 8-22, 1965.
7. FAIGLE, J. W. & KEBERLE, H. - The metabolic fate of CIBA 32 644-Ba. Therapeutique Nouvelle de la bilharziose et de l'amebiase. Acta Tropica, supplementum 9: 8-22, 1965.
8. LAMBERT, C. R. & CRUZ FERREIRA, F. S. - Resultats du premier essal thérapeutique de la bilharziose vésicale par le CIBA 32 644-Ba. Bull. World Health. Org., 32: 73, 1965.
9. LAMBERT, C.R. - Chemotherapy of Experimental Schistosoma mansoni Infections with a Nitrothiazole Derivate, CIBA 32 644-Ba. Ann. Trop. Med. and Parasitology, 58: 292, 1964.
10. LAMBERT, C.R., SINARI, U.S.P. & TRIPOD, J. - Action of CIBA 32 644Ba on Spermatogenesis in Laboratory Animais. Acta Tropica, 22: 115, 1965.
11. PETERS, W. - Comunicação pessoal, 1966.
12. PRATA, A.; MACHADO, R. & MACEDO, V. - Treatment of Schistosomiasis mansoni with a new nitrothiazole derivate CIBA 32 644-Ba. Acta Tropica, supplementum 9: 180-87, 1965.
13. PRATES, M. D. & FRANCO, A.L.T. - Action de CIBA 32 644-Ba sur la spermatogéneSc. Etude preliminaire. Acta Tropica, supplementum 9: 287-88, 1965
14. RODRIGUES DA SILVA, J. - CIBA 32 644-Ba and Spermatogenesis in Man. Preliminary Results. Acta Tropica supplementum 9: 283-286, 1965.
15. RODRIGUES DA SILVA, J. - A clinical trial of CIBA 32 644-Ba in Schistosomiasis mansoni. Acta Tropica, supplementum 9: 177-179, 1965.
16. ROSI, D.; PERUZZOTTI, G.; DENNIS, E. W.; BERBERIAN, D.A.; FREELE, H. & ARCHER S. - A New, Active Metabolite of "Miracil D". Nature, 208: 1005-1006, 1965.
17. SADUN, E.H., BRUCE, J.I.; MOOSE, J. W. & MCMULLEN, D. B. - The Prophylactic and Curative Activity of a Nitrothiazole Derivate, l-5-nitro-2- oxo-tetra-hydro-imidazole, in Rhesus Monkeys Experimentaly Infected with S. mansoni and in Mice Infected with S. japonicum Apresentado no Simpósio de Lisboa, junho, 1965.
18. STRIEBEL, H. P. & KRADOLFER, F. - Mode of action of CIBA 32 644-Ba in Experimental Schistosomiasis. Acta Tropica, supplementum 9: 54-58, 1965.
19. WILHELM, M. & SCHMIDT, P. - Eine neue gegen Bilharziose und Amoebiase wirksame Verbindung. Experimentia, 20: 452, 1964.

Datas de Publicação

Publicação nesta coleção
07 Ago 2013
Data do Fascículo
Abr 1967

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ARGENTO, C.A.; NEVES, P.F.; GALVAO, F. A. & RODRIGUES DA SILVA, J. - O composto CIBA 32 644-Ba (Aminonitrotiazol) no tratamento da Esquitossomose mansoni. Fôlha Médica. Rio, 5:7, 1965.

[2] 2. BARANSKI, M .C. - Comunicação pessoal, 1966.

[3] 3. BARANSKI, M.C. & SILVA, A.F. - Ineficácia do tratamento da esquistossomose mansônica pelo A 16 612 (n(3- cloro-4-metilfenil) - n'(4-t'-amilfenoxi-hexametileno) cloridrato de piperazina. Trabalho apresentado ao XVI Cong. Bras. de Hig., Curitiba, 1966.

[4] 4. BUEDING, E. & SCHILLER, E. - Mechanism of action of antischistosomal drugs. Abstracts of the International Pharmacological Congress, São Paulo, soai, 1966.

[5] 5. CARVALHO NETO, Comunicação pessoal, 1966.

[6] 6. COUTINHO, A.; LIMA, C.A. & ALVES C. - A clinical trial of CIBA 32 644- Ba. Therapeutique Nouvelle de la bilharziose et de l'amebiase. Acta Tropica, supplementum 9: 8-22, 1965.

[7] 7. FAIGLE, J. W. & KEBERLE, H. - The metabolic fate of CIBA 32 644-Ba. Therapeutique Nouvelle de la bilharziose et de l'amebiase. Acta Tropica, supplementum 9: 8-22, 1965.

[8] 8. LAMBERT, C. R. & CRUZ FERREIRA, F. S. - Resultats du premier essal thérapeutique de la bilharziose vésicale par le CIBA 32 644-Ba. Bull. World Health. Org., 32: 73, 1965.

[9] 9. LAMBERT, C.R. - Chemotherapy of Experimental Schistosoma mansoni Infections with a Nitrothiazole Derivate, CIBA 32 644-Ba. Ann. Trop. Med. and Parasitology, 58: 292, 1964.

[10] 10. LAMBERT, C.R., SINARI, U.S.P. & TRIPOD, J. - Action of CIBA 32 644Ba on Spermatogenesis in Laboratory Animais. Acta Tropica, 22: 115, 1965.

[11] 11. PETERS, W. - Comunicação pessoal, 1966.

[12] 12. PRATA, A.; MACHADO, R. & MACEDO, V. - Treatment of Schistosomiasis mansoni with a new nitrothiazole derivate CIBA 32 644-Ba. Acta Tropica, supplementum 9: 180-87, 1965.

[13] 13. PRATES, M. D. & FRANCO, A.L.T. - Action de CIBA 32 644-Ba sur la spermatogéneSc. Etude preliminaire. Acta Tropica, supplementum 9: 287-88, 1965

[14] 14. RODRIGUES DA SILVA, J. - CIBA 32 644-Ba and Spermatogenesis in Man. Preliminary Results. Acta Tropica supplementum 9: 283-286, 1965.

[15] 15. RODRIGUES DA SILVA, J. - A clinical trial of CIBA 32 644-Ba in Schistosomiasis mansoni. Acta Tropica, supplementum 9: 177-179, 1965.

[16] 16. ROSI, D.; PERUZZOTTI, G.; DENNIS, E. W.; BERBERIAN, D.A.; FREELE, H. & ARCHER S. - A New, Active Metabolite of "Miracil D". Nature, 208: 1005-1006, 1965.

[17] 17. SADUN, E.H., BRUCE, J.I.; MOOSE, J. W. & MCMULLEN, D. B. - The Prophylactic and Curative Activity of a Nitrothiazole Derivate, l-5-nitro-2- oxo-tetra-hydro-imidazole, in Rhesus Monkeys Experimentaly Infected with S. mansoni and in Mice Infected with S. japonicum Apresentado no Simpósio de Lisboa, junho, 1965.

[18] 18. STRIEBEL, H. P. & KRADOLFER, F. - Mode of action of CIBA 32 644-Ba in Experimental Schistosomiasis. Acta Tropica, supplementum 9: 54-58, 1965.

[19] 19. WILHELM, M. & SCHMIDT, P. - Eine neue gegen Bilharziose und Amoebiase wirksame Verbindung. Experimentia, 20: 452, 1964.