Exciting new discoveries about the PDE6 enzyme may someday help to inform the development of erectile dysfunction drugs without visual side effects.
Among the more common side effects of Viagra and other erectile dysfunction drugs are temporary visual disorders. These can include a bluish tint to vision or an increased sensitivity to light. These visual disorders are mild and tend to disappear with continued use of the drug.
However, for some users, such vision problems can be disconcerting, so researchers have been trying to better understand how ED drugs trigger such alterations in normal vision.
Viagra Is a PDE5 Inhibitor
Viagra and the other ED drugs introduced in its wake belong to a family of drugs known as PDE5 inhibitors. To temporarily improve blood flow to the penis, they sideline the phosphodiesterase-5 enzyme, which can interfere with optimal blood flow.
While the developers of PDE5 inhibitors tried very hard to limit the effects of their drugs to the PDE5 enzyme, it appears that they can sometimes interact with other PDE enzymes that have no real part in erectile function but do control other bodily functions.
PDE6 Plays Key Role in Vision
Such is the case with the PDE6 enzyme, which plays a critical role in human vision.
To better understand the cross-reactivity of various PDE inhibitors, researchers from the University of California, Irvine, joined with researchers from Ohio’s Case Western Reserve University and Switzerland’s University of Basel. Using single-particle cryo-electron microscopy, the researchers were able for the first time to visualize the full-length structure of the PDE6 enzyme. Their findings were published in the February 2019 issue of Science Advances.
From this first look at the entire structure of the PDE6 enzyme, researchers spotted several unique features that may allow pharmaceutical researchers in the future to develop PDE inhibitors that are more selective and less likely to interact adversely with other PDE enzymes.
Hope for the Future
Men using PDE5 inhibitors to treat erectile dysfunction sometimes experience visual side effects that the research team believes result from the drugs’ inadvertent effects that inhibit the PDE6 enzyme. Given this greater understanding of the PDE6 enzyme’s structure, it’s possible that future PDE5 inhibitors can avoid this interaction and thus eliminate visual side effects.
Among the newly discovered features of the PDE6 enzyme’s structure, said lead author Sahil Gulati, “were some very promising regions of PDE6 that resemble fish-hooks.” He went on to say that these regions appear to control PDE activity. Gulati expressed the hope that drug development companies in the future could eliminate or at least reduce unwanted side effects of certain PDE inhibitors by targeting the fish hook-like region.
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