[Potentiation of the antiviral activity of daunomycin by desmethylimipramine].
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Biomedical subjects
Publications and source records attributed to R Bossa.
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Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens.
The in vitro activity of a chemotherapeutic agent, sulfimidazole (SIZ), obtained by combining two molecules belonging to groups of extremely different antibacterial drugs, p-aminobenzene sulfonamide and a derivative with a 5-nitroimidazole ring, was studied. In association with trimethoprim, SIZ induces an intense synergistic antibacterial effect on gram-negative and gram-positive aerobic microorganisms and Clostridia. The results show that, in SIZ, the activity of each starting molecule remains unchanged providing that its structure-action relationship is kept intact.
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The effect of the H2-receptor antagonist, nizatidine, on neuromuscular transmission was investigated using sciatic nerve-gastrocnemius muscle preparations of rat in vivo. Nizatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and the aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on preparations stimulated at high frequency. The neuromuscular blockade induced by nizatidine is reversed by 4-aminopyridine but not by dimaprit.
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We have investigated the effects of the H2 receptor antagonist famotidine on the neuromuscular transmission by using the sciatic nerve--gastrocnemius muscle preparation of rat in vitro. Famotidine, administered by I.V. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotics. Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency. The neuromuscular blockade induced by famotidine is reversed by 4-aminopyridine but not by dimaprit. Similar results have previously been obtained with cimetidine.
We have reported that the H2 receptor antagonists, cimetidine and ranitidine, interfere with neuromuscular transmission on the isolated phrenic nerve--diaphragm preparation of the rat in vitro and we have suggested that the neuromuscular blockade produced could be ascribed to an action at presynaptic level by competing calcium ions unrelated to their specific effects on H2 histamine receptor: in fact, neuromuscular blockade was reversed by calcium and 4-aminopyridine but not by neostigmine or dimaprit. In the present study these results are confirmed in vivo on the sciatic nerve-gastrocnemius muscle preparation of the rat.
This study describes the effects of some anthracyclines (adriamycin, 4-epiadriamycin and esorubicin) on isolated, electrically driven left guinea pig atrium in normodynamic or hypodynamic (Tyrode solution with 0.1 g/1 CaCl2) conditions. Exposure for 60' to the anthracyclines caused a depression of contractile force and of maximal rate of tension development (df/dt). The statistical analysis of data showed an equivalent inhibitory effect between adriamycin and esorubicin, whereas 4-epiadriamycin has in normodynamic conditions greater negative inotropic effects significantly different from that of the two other drugs. Thus the lower toxicity of 4-epiadriamycin observed in vivo by other authors may probably be imputed to a lower concentration of the drug in the heart. The cardiac depressant effects induced by anthracyclines in vitro, as previously reported, are antagonized by new cardiotonic agents whose mechanism of action can be related to an increase in calcium activity in myocardial tissue.
Recently several non catecholamine, non glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate anthracycline toxicity, we have previously reported that these compounds reduced the negative inotropic effect of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent synthesized and studied by us: 2,3-Dihydro-6- (2,5-dimethoxyphenyl) imidazo [2,1-b]thiazole (VA-5), the most active of a series of 32 compounds with imidazo [2,1-b] thiazole and thiazoline moiety. Exposure for 60 to adriamycin (100 micrograms/ml) of electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions, caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of adriamycin are antagonized by VA-5 (100 micrograms/ml).
Synthesis of 2,6-Bis[bis(2-chloroethyl) amino]-4,8-dipiperidinopyrimido[5,4-d] pyrimidine, a derivative of dipyridamole, was carried out by treating dipyridamole with thionyl chloride. Cytotoxic activity of this compound was assessed using cultured P388 leukaemia cells and HeLa cells. The compound inhibited the colony-forming ability of HeLa cells and showed a cytotoxicity on P388 cells comparable to that of other alkylating drugs (chlorambucil and CCNU).
The in vitro antibacterial activity of quinolone compounds was assessed on strains of Pseudomonas aeruginosa isolated from clinical infections. The bactericidal effect of quinolones was high and their respective antibacterial properties with adriamycin remained unimpaired on strains both sensitive and resistant to betalactam and aminoglycoside antibiotics. The cytotoxic effect of the combination of adriamycin and quinolones was determined in cultured P388 leukemia cells: no interference with the cytotoxic activity of adriamycin was observed.