Two potentially significant advancements in drug therapy—both sought for years—were reported this month: an antibiotic and an anti-obesity drug.
A new potential antibiotic was discussed yesterday in an article in ScienceDaily. It kills a broad group of bacteria, including methacillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant bacteria. At the present time, there is no antibiotic available that is completely effective against these microbes.
Bacterial resistance to antibiotics emerged as a significant problem not long after antibiotics were developed. Resistance to penicillin, which first appeared in 1947, was overcome with the introduction of the penicillin-like compounds, methacillin and oxacillin. But then MRSA, a type of Staphylococcus resistant to those drugs, too, appeared in 1961. Until the 1990s, only one drug, vancomycin, could be counted upon to vanquish the resistant bacteria. But eventually vancomycin-resistant bacteria appeared, too. Despite the development of new antibiotics that work against some resistant organisms (e.g., linezolid), there is none available now that works against all of them.
The newly reported antibiotic was derived from the soil bacterium, Microbispora corallina, and is called microbisporicin. It is effective against MRSA, vancomycin-resistant microorganisms, and another difficult-to-treat bacterium that causes severe diarrhea, Clostridium difficile. Microbisporicin is presently undergoing tests in animals. If it passes the tests, it should move into human clinical trials before long.
Another pharmacotherapy advancement, one that involves a potential anti-obesity drug, was reported earlier this month. The new drug is related to rimonabant (Acomplia, Zimulti, et al.), a weight-loss drug that works by blocking cannabinoid receptors. Activity of the endogenous cannabinoid system of neurons is known to induce hyperphagia in animals, an effect which is perhaps related to the notorious “marijuana munchies” observed in humans. Rimonabant counteracts this effect, and human studies have shown that the drug can produce significant weight loss [pdf file] of up to 7 kg in a year, along with improvements in cholesterol and glucose metabolism. But it was also found that rimonabant is associated with a high rate of severe psychiatric adverse effects, including depression and suicidality. Consequently, the drug was not approved in this country.
The new medication is designated TM38837, because it is not yet named. Christian Elling of the Danish drug company, 7TM Pharma, discussed it at the recent International Congress on Obesity in Stockholm. Although it blocks the same cannabinoid receptors as rimonabant, TM38837 does not cross the blood-brain barrier and penetrate into the brain to the same degree. It apparently acts mainly at receptors in the peripheral nervous system. Elling said the compound has produced significant weight loss in studies in mice and rats. It is hoped that the drug will produce weight loss in human studies, too, and because TM38837 does not act in the brain, it will not have the severe psychiatric adverse effects that prevented approval of rimonabant.
The history of weight-loss drugs shows that most medications were beset with significant problems. As one example, dextroamphetamine (Dexedrine), one of the first drugs prescribed for weight loss, caused insomnia, depression and paranoia, and it was addictive. Another example was the drug combination of phentermine and dexfenfluramine, known as Fen-Phen, which was popular for several years in the 1990s. However, dexfenfluramine was withdrawn from the market in 1997 for causing heart valve defects.
At present there are no substantially effective weight loss medications on the market. If TM38837 demonstrates the efficacy and safety that is hoped for, it could indeed become a breakthrough medication.