Selective androgen receptor modulator

Selective androgen receptor modulators or SARMs are a novel class of androgen receptor ligands. (The name follows the terminology currently used for similar molecules targeting the estrogen receptor, "selective estrogen receptor modulators," such as Tamoxifen.)

Comparison to testosterone

Currently used androgens for male hormone replacement therapy are typically injectable or skin delivery formulations of testosterone or testosterone esters. Injectable forms of testosterone esters (such as testosterone enanthate, propionate, or cypionate) produce undesirable fluctuations in testosterone blood levels, with overly high levels shortly after injection and overly low afterwards. Skin patches do provide a better blood level profile of testosterone, but skin irritation and daily application still limit their usefulness. Oral androgens are not currently used due to concerns about liver toxicity.

SARMs provide the opportunity to design molecules that can be delivered orally, but that selectively target the androgen receptors in different tissues differently. The goal of research in this area is to allow a customized response: tissues that are the target of the therapy will respond as they would to testosterone; other tissues where undesirable side effects are produced will not.

electivity in men

For example, if the target is bone growth in elderly men with osteopenia or osteoporosis, but with no overt signs of hypogonadism, a SARM targeting bone and muscle tissue, but with lesser activity on the prostate or testes would be more desirable.cite journal | author = Ke HZ, Wang XN, O'Malley J, Lefker B, Thompson DD | title = Selective androgen receptor modulators--prospects for emerging therapy in osteoporosis? | journal = J Musculoskelet Neuronal Interact | volume = 5 | issue = 4 | pages = 355 | year = 2005 | pmid = 16340136 | doi = | issn = | url = http://www.ismni.org/jmni/pdf/22/23THOMPSON.pdf ]

electivity in women

A SARM for women would ideally stimulate bone retention, or libido and other sexual function that androgens can influence, without negative side effects such as development of male gender characteristics (virilization), increased LDL/HDL ratios, liver disfunction, and so forth.cite journal | author = Negro-Vilar A | title = Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium | journal = J. Clin. Endocrinol. Metab. | volume = 84 | issue = 10 | pages = 3459–62 | year = 1999 | pmid = 10522980 | doi = 10.1210/jc.84.10.3459 | issn = ]

Examples

One proposed agent is "JNJ-28330835".cite journal |author=Allan GF, Tannenbaum P, Sbriscia T, "et al" |title=A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats |journal=Endocrine |volume=32 |issue=1 |pages=41–51 |year=2007 |pmid=17992601 |doi=10.1007/s12020-007-9005-2]

Another is known as "S-4".cite journal |author=Kearbey JD, Gao W, Narayanan R, "et al" |title=Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats |journal=Pharm. Res. |volume=24 |issue=2 |pages=328–35 |year=2007 |pmid=17063395 |doi=10.1007/s11095-006-9152-9]

ee also

* Selective estrogen receptor modulator
* Selective progesterone receptor modulator

References