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.

4-Aminopyridine↗

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"In vitro" study of sulfimidazole, trimethoprim and fluoroquinolones in traveller's bowel infections.

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Anti-Bacterial Agents↗

PubMedDate not supplied

The effect of famotidine on neuromuscular transmission.

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.

Animals↗

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The effect of H2 receptor antagonists on neuromuscular transmission.

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.

Animals↗

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Cardiotoxicity of anthracyclines.

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.

Animals↗

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Reduction of adriamycin cardiotoxicity by a new cardiotonic agent.

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).

Animals↗

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Synthesis and cytotoxic activity of a new alkylating derivative of dipyridamole.

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).

Alkylating Agents↗

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The bactericidal effect on Pseudomonas strains of adriamycin associated with quinolones.

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.

Ciprofloxacin↗

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Antibacterial and cytotoxic effect of ceftazidime-mitoxantrone association.

Microbial infections are a major problem in tumor-bearing and in immunocompromised patients. In such conditions it is of paramount importance to know the possible interactions between anti-tumor and antimicrobial drugs. In the present work we investigated the relationship between Ceftazidime and Mitoxantrone. Ceftazidime and Mitoxantrone were tested alone and in combination for antibacterial activity against different strains of Gram- and Gram+ bacteria. The cytotoxic effect of combination Mitoxantrone-Ceftazidime was determined in cultured P388 leukemia cells. No interference with the antibacterial activity of Ceftazidime or with the cytotoxic activity of Mitoxantrone was observed.

Animals↗

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Bactericidal and cytotoxic effect of combination of norfloxacin and 5-fluorouracil.

Using the agar dilution technique, we examined the in vitro antibacterial activity of 5-fluorouracil and norfloxacin alone and in association against several bacterial strains. When administered in association, the two drugs did not antagonize each other in tests carried out on strains both sensitive and resistant to penicillins, cephalosporins, aminoglycosides, tetracyclines; furthermore their respective antibacterial properties remained largely unimpaired. The cytotoxic activity and the antitumoral effect of a combination of 5-fluorouracil and norfloxacin was determined in cultured tumor cells, and in mice bearing Ehrlich ascites carcinoma. No significant interference with the cytotoxic activity and antitumoral activity of 5-fluorouracil was observed.

Animals↗

PubMedDate not supplied

Reduction of 4-epiadriamycin cardiotoxicity by milrinone, a new cardiotonic agent.

Recently, several non-catecholamine, non-glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole and milrinone. Milrinone, a close analogue of amrinone, is about 30 times more potent than amrinone. In attempts to alleviate anthracyclines toxicity, we have previously reported that amrinone and sulmazole reduced the negative inotropic effect of adriamycin and 4-epiadriamycin in isolated guinea pig atria. The present study reports the effects of 4-epiadriamycin on electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions. Exposure for 60' to 4-epiadriamycin (100 micrograms/ml) caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of 4-epiadriamycin are antagonized by milrinone at 20 micrograms/ml.

Animals↗

PubMedDate not supplied

Cytotoxic activity of a series of heteroaryl-ONN-azoxy-sulphones and aryl sulphonylhydrazones.

Synthesis of heteroaryl-ONN-azoxysulphones and pyrazolyl-ONN-azoxycyanides was carried out by the action of the appropriate reagents on the corresponding nitroso derivatives. Pyrazolyl-ONN-azoxyamides were obtained by hydrolysis of the corresponding cyanides. Synthesis of the arylsulphonylhydrazones was carried out by reacting R-substituted phenyl-sulphonylhydrazines on the isomers of methylfuroxancarbaldehyde. Cytotoxic activity was assessed on HeLa cells. Some of the compounds tested inhibit the colony-forming ability of the tumor cells at low concentrations.

Antineoplastic Agents↗

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Cytotoxic activity of aryl and heteroaroxylazoxy derivatives.

Synthesis of aryl and heteroarylazocyanides, azoxyesters and azoxysulphones, was carried out by the action of appropriate reagents on the corresponding nitroso derivatives and arylazoxyamides were obtained by hydrolysis of the corresponding azoxycyanides. Cytotoxic activity was assessed utilizing cultured P388 leukemia cells. Most of the compounds tested showed a marked cytotoxicity at concentrations below 1 micrograms/ml.

Animals↗

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Sensitivity to anthracyclines in P388/dx leukaemia cells.

It has been demonstrated previously that neoplastic cells with reduced oxygen consumption are more sensitive to doxorubicin8. We have examined the relationship between doxorubicin sensitivity and oxygen consumption of P388 murine leukaemia cell line (P388) and of a doxorubicin resistant subline (P388/dx). Oxygen utilization by P388/dx cells was higher than that found in the sensitive line. A variety of calcium antagonists, including channel blockers and intracellular antagonists (verapamil, trifluoperazine, dantrolene, TMB-8, nitrendipine) or membrane acting drugs (lucensomycin), enhanced the cytotoxic activity of doxorubicin in P388 and markedly in P388/dx subline. This action was accompanied by a reduction of oxygen consumption more pronounced in the resistant cells. These findings emphasizé the correlation between oxygen uptake, instead of calcium dependent processes, and doxorubicin responsiveness. The calcium ionophores A 23187 failed to alter doxorubicin activity in P388 and P388/dx leukaemia.

Animals↗