Respiratory problem trials

Almitrine (244), which is used to treat respiratory problems, was used as a lead compound to develop triazine derivatives as potent modulators of multidrug resistance in cancer therapy <92JMC248i>. Triazine (245) was selected as the best candidate for development and is currently in phase 1 clinical trials. 

It was found, when an attempt was made to conduct ship trials that the paint applier would be required to wear long sleeves, gloves, safety glasses, and a protective face shield. It is also a requirement that an eyewash fountain be nearby. These requirements were imposed because acrylates are skin, eye and respiratory tract irritants, but the problem lies mostly with the acrylated reactive diluent rather than with the acrylated resin (2,3). To avoid these problems, tests have been performed with use of trimethylolpropane trimethacrylate (TMPTMA) as a replacement for TMPTA. TMPTMA has been shown to be much less of an irritant than TMPTA, and is used in dental restorations. 

Although oseltamivir (1, Tamiflu) has risen to be a superstar in the wake of the avian flu, zanamivir (2, Relenza) seems to be underappreciated by the world medical society, possibly because zanamivir (2) is a mouth spray and may cause problems for patients with breathing problems such as asthma. In reahty, zanamivir (2) has a great tolerability, similar to that of placebo, for otherwise healthy adults and higher-risk patients such as the elderly and children. Recommended doses (10 mg twice daily for 5 days) of zanamivir (2) did not adversely affect pulmonary function in patients with respiratory disorders in a well-controlled trial, although there have been reports of bronchospasm and/or decline in respiratory function. 

As with influenza, the brevity of the incubation period and the fact that by the time the first symptoms appear, the virus will already be present in large amounts, means that prophylaxis and treatment are difficult. Add to this the fact that the cold may be due to another type of virus, for example, an adenovirus (a DNA virus) or a respiratory syncitial virus, and the problems appear insuperable. And indeed, at present, no drugs have reached the marketplace. The rhinoviruses are RNA-(+)-viruses and have two principal viral enzymes an RNA polymerase and a protease, but although a number of potential enzyme inhibitory drugs have been evaluated in clinical trials, none has reached the marketplace. 

The adverse events profile for escitalopram is similar to that observed with Ri-citalopram in both major depression and anxiety disorders. Discontinuation rates due to adverse events were similar in patients receiving escitalopram or placebo in several trials. Nausea and ejaculatory problems were reported in both fully published trials in patients with major depression. In addition, diarrhea, insomnia, dry mouth, headache, and upper respiratory tract infections were experienced by patients receiving escitalopram, although the incidence of these events was not significantly higher than in patients receiving placebo. The recommended dose of escitalopram for the treatment of major depression is 10 mg/day, which, depending on the individual patient response, may be titrated up to 20 mg/day. 

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