Women
can choose from a wide selection of birth control methods, including numerous
oral contraceptives, but there's never been an analogous pill for men.
That's
not for lack of trying: For many years, scientists have attempted to formulate
a male pill. Finally, a group of researchers has taken a step toward that goal
by tweaking some experimental compounds that show promise.
The
researchers present their work today at the 251st National Meeting &
Exposition of the American Chemical Society (ACS).
One
compound that's been studied as a potential male contraceptive is testosterone.
"At certain doses it causes infertility," says Jillian Kyzer, a
graduate student working on the topic. "But at those doses, it doesn't
work for up to 20 percent of men, and it can cause side effects, including
weight gain and a decrease in 'good' cholesterol."
Bringing
any male contraceptive to market requires it to satisfy several requirements,
explains Kyzer's team leader, Gunda I. Georg, Ph.D., who is based at the
University of Minnesota College of Pharmacy. It would have to be soluble so it
could be taken by mouth. It would start working fairly quickly, and it wouldn't
diminish libido. It would be safe even if taken for decades. And because some
users would eventually want to have children, its impact on fertility would be
reversible, with no lingering ill effects on sperm or embryos. "That's a
very high bar for bringing a male contraceptive to market," Georg points
out.
These
hurdles have driven many investigators from the hunt, yet Georg's team
perseveres. "It would be wonderful to provide couples with a safe
alternative because some women cannot take birth control pills," she says.
Drug
companies, including Bristol-Myers Squibb (BMS), have created some experimental
male contraceptives, but these too have drawbacks, Kyzer says. For instance,
one of the company's test compounds is good at inhibiting fertility but isn't
very soluble, so it can't be taken by mouth. "No one wants to inject
themselves with a needle once a day or once a week for most of their
lives," she notes.
Another
Bristol-Myers Squibb experimental compound can be taken orally but isn't very
selective in terms of its cellular targets in the body. That means the compound
not only interacts with the retinoic acid receptor-α, which is involved in male
fertility, but also with two other retinoic acid receptors that are unrelated
to fertility. That flaw could cause side effects.
Kyzer
and several of her colleagues are creating numerous substances that are similar
in their chemical structure to the Bristol-Myers Squibb compounds. Although the
optimal contraceptive for men remains elusive, Georg's team has made some
progress. For example, the researchers are gaining a better understanding of
how tweaks to the chemical structure of their test compounds affect the
substances' cellular interactions in the body. One of those tweaks added a
polar group to the molecule, which made the test compounds more soluble. Another
tweak replaced an amide bond in the BMS compound with slightly different bonds
that are known in the field of medicinal chemistry to mimic an amide bond. As
intended, that change improved the test compounds' stability, meaning they
would last longer in the body. Unfortunately, both types of modifications also
reduced the specificity of the compounds for the intended retinoic acid
receptor-α target.
The
group continues to refine the chemical structures to achieve the ultimate
balance of solubility, specificity and stability as they aim to design a better
male pill. They are now investigating hybrid compounds that incorporate
scaffolds and structural features from several other compounds known to
interact with the retinoic acid receptor.
Source:
sciencedaily
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