Prison Architect Is Prepared To Expand Its Psych Ward: Wardens Edition – The Hear UP

Androgenic therapy with injectable, oral and more recent transdermal drugs has been available to doctors for many years to treat a variety of male diseases. To a lesser extent, its application has been extended to some female indications. Unlike female sex hormone therapies, which are widely used and widely used in the field of hormone replacement, reproductive disorders, gynecological cancers and contraception, androgen therapy is not widely used. Recent progress has clearly demonstrated that androgen therapy will undergo a major change, both in the scope and in the range of applications that can benefit from this upcoming progress.

Various factors contributed to this change. First, the significant advances in hormonal replacement therapy (HRT) in postmenopausal women and the extension and application of HRT for the treatment and prevention of serious diseases such as osteoporosis, cardiovascular disease, breast cancer, mood and cognition, have clearly demonstrated value in new HRT therapies to improve womens health (2-4) and extrapolation emphasize the potential for similar approaches to the treatment of mens health problems.

Second, the development and commercialization of new selective estrogen receptor modulators (SERMs) has provided both pre-clinical and clinical evidence that we can develop molecules with high levels of tissue selectivity targeting the estrogen receptor to eliminate and maintain unwanted side effects (and future). to improve the positive, protective effects of selective transcriptional receptor activation (3-7).

Third, major advances in our understanding of the activation and function of nuclear receptors have laid the molecular foundation for new drug development efforts to develop a new generation of tissue-selective molecules that target steroid and other nuclear receptors. The proof-of-concept of tissue selectivity has now been extended to many compounds that interact with different nuclear receptors such as: Estrogen (ER), progesterone (PR), androgen (AR), retinoid (RAR / RXR) and peroxisome proliferation, including activated receptors (PPARs) (6-11).

With the information described above, we were able to register a developmental trajectory and to profile the desired activity and selective indications for a new class of molecules focused on the androgen receptor. In the following we briefly describe the molecular mechanisms that underlie the potential for selective modulation of AR by different ligands, and the possibilities offered by new SARMs for therapies for broad and selective applications of androgen therapy in both men and women.

Molecular progress in the structure and function of AR: a key to releasing tissue selectivity

The AR is a transcription factor and belongs to the extensive family of nuclear receptors. As such, it shares substantial structure homology with the other members of the family, including specific protein subdomains that activate or suppress gene activity. These different mechanisms contribute to the combinatorial recruitment and activity of coactivators and co-depressors to enable selective regulation of individual genes in certain tissues by the AR.

Since different ligands can provide a variety of different combinatorial transcriptional regimens in different tissues and cells, the development of SARMsToday with intrinsic partial agonistic activity offers a unique opportunity to develop new therapeutics with different activity profiles.

The different sets of molecules contain individual members who have selective preferences for specific tissues or activities (e.g., Trophic in muscles, strong or very weak gonadotropin feedback) and very different activity ratios in sexual accessory tissues (prostate, seminal vesicles) compared to other peripheral tissues (ie muscles) or central

Currently used androgenic replacement therapy formulations are broadly limited to injectable or testosterone or testosterone ester skin release formulations. Commercially available injectable forms of testosterone esters (such as testosterone anthogenate, propionate or cypionate) cause unwanted fluctuations in testosterone blood levels with supraphysiological concentrations at an early stage and subnormal levels towards the end of the period prior to the next injection, resulting in an unsatisfactory profile and in some cases unwanted side effects.

Although dermal patches offer a better testosterone blood profile, skin irritation and daily use limit the benefit and acceptance of this type of therapy (1, 20-22). Oral preparations such as fluoxymesterone and 17-methyltestosterone are not currently used because there are concerns about liver toxicity associated with the 17-alkyl group and their efficacy is slightly lower. Therefore, these compounds are considered outdated (1, 20) and do not represent a viable form of therapy.

The discovery and development of SARMs offers the possibility to design molecules that are not only orally active, but focus on AR in different tissues to induce the desired activity for each of the most important indications that benefit from androgen therapy. The desired activity profile of new SARMs is described in Table 1. For simplicity, we have listed the desired activity in tissues or specific parameters for a specific indication (i.e., male hypogonadism) in addition to a category for selected indications. The latter offers a series of choices for the design of molecules that can respond to specific needs in the treatment of various diseases.

Therefore, we imagine that an ideal SARM for the treatment of primary or secondary male hypogonadism (Table 1) has the following profile: orally active, ideally with a pharmacokinetic profile consistent with once-daily administration and stimulating prostate and seminal vesicles. and other canned sexual accessory tissues corresponding to those required to increase muscle mass and strength and lean body mass, to promote bone growth and to maintain/restore libido, virilization and male habit.

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Prison Architect Is Prepared To Expand Its Psych Ward: Wardens Edition - The Hear UP