Compatible alternative: researchers may have discovered an alternative to common opioid analgesics – in a fungus. Drugs in a penicillium species act in a different way than conventional opioids and may have less dangerous side effects. An agent developed on the model of these fungal substances has been shown to be as effective as morphine in experiments on mice.
Many patients with pain can only provide relief to opioids. These opium derivatives attach to certain receptors of the spinal cord and brain and thus block the transmission of pain stimuli. But the use of funds is not without problems: opioids can cause serious side effects and addiction in no time – overdoses always end up being fatal.
For this reason, researchers have long been looking for alternatives more compatible with the painkillers used until now. Zoltan Dean of the University of Queensland at Brisbane and his colleagues may have found something in the wild: a previously unknown mushroom of the genus Penicillium.
Surprising discovery in the mud
Until now, species of this genus were known mostly for the penicillin antibiotics that they produce. But at least one representative of these fungi also seems to carry interesting substances for the treatment of pain. Scientists have discovered this species in the mud of a Huan Valley water plan, in the Australian state of Tasmania.
In-depth investigations of Penicillium species called Mst-MF667 led Zoltan and his colleagues to discover three tetrapeptides. The peculiarity: these peptides, each composed of four amino acids, have a very rare chiral structure with straight amino acids. And: they are similar to the known endomorphins of humans – endogenous opioids that act on μ receptors.
Other signaling pathway, less side effects
Active substances similar to endomorphins have long been considered as a possible approach to analgesics with fewer side effects and less dependence potential than common opioid drugs. The researchers took advantage of their discovery to develop a new analgesic based on peptides found in the fungus.
In particular, the result called bilorphine is that it exerts its effect on μ-opiod receptors via a signaling pathway different from that of traditional opioids. Zoltan's team says that it activates the protein G signaling pathway, a mechanism that appears to be associated with a reduction in side effects typical of conventional opioids.
As powerful as morphine
However, other experiments on mice initially revealed that the active substance in the body did not produce the desired effect. However, the addition of a sugar unit resulted in the activation of the agent. In this modified form, the active ingredient is called bilactorphine. It can be taken orally depending on the results and is similar to morphine.
That the bilactorphine actually has the stuff of new morphine without shaded sides, remains to be seen in the future. If this hope is realized, the consequences will be heavy: "If we succeed and we market a new drug one day, it will probably reduce the risk of fatal overdose and other side effects," says co-author MacDonald Christie from the University of Sydney.
Source of new drugs for pain
At the same time, the researchers' research indicates that microorganisms such as fungi are a valuable source of pain medication: "Microbes could be a source of new painkillers that have not been exploited before and deserve to be examined more closely, "concluded the team. (Proceedings of the National Academy of Sciences, 2019, doi: 10.1073 / pnas.1908662116)
Source: University of Sydney