Hi guys,
i noticed there was no information on these boards about SARMs [Selective Androgen Receptor Modulators]. So i decieded to sum up what I know about the topic and hope that some of you will chime in, so that we can get a little more info on that topic.
A SARM is a substance which excerts a primary anabloic effect and only a very weak androgenic effect. In some cases it even has an AR-Agonist behavior.
The first SARM was discovered in 1998. Scientist could observe a high affinity for the androgen receptor in this compound (10 times higher than testosterone and equal to DHT).
Based on these findings research continued and finally the first REAL SARM was discoverd. SARMs are tissue selective and exert its effects mostly in anabolic tissue (i.e. muscle) whereas androgenic tissue (i.e. prostate) is affected only to a minor extend. Moreover several SARM also have a positive impact on bone densitiy and cartilage not unlike deca.
The first developed SARM (S-1) was 3-(4-Fluorophenoxy)-2-Hydroxy-2-Methyl-N-[4-Nitro-3-5 (Tr***uoromethyl)Phenyl]-Propanamid. (see structure in attachment)
S-1 could maintain bodyweight and muscle mass in castrated rats whereas only a minor increase in prostate weight was observed. Moreover S-1 even blocks the androgenic activity of testosterone in androgenic tissue by taking up its receptors but not activating them. Newer SARMS like S-1; S-2; S-3 and S-4 have varrying degrees of androgenic activity (3-15%) in comparsion to DHT but a 100% anabolic activity.
Moreover it is interesting to now that S-1 and S-4 do not cause significant LH suppression at all while maintaing the anabolic activity of Tesosterone Propionate.
Pharmacodynamics of Selective Androgen Receptor Modulators (SARMs)
Donghua Yin 1, Wenqing Gao 1, Jeffrey D. Kearbey 1, Huiping Xu 1, Kiwon Chung 2, Yali He 2, Craig A. Marhefka 2, Karen A. Veverka 3, Duane D. Miller 2, James T. Dalton 1*
1 The Ohio State University 2 The University of Tennessee 3 GTx, Inc.
* Address correspondence to: E-mail: [email protected]
Abstract
The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacologic activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with Ki values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacologic activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, while levator ani muscle weight was used as a measure of anabolic activity. The maximal response (Emax) and dose for half-maximal effect (ED50) were determined for each compound and compared to that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant LH or FSH suppression at doses near the ED50. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.
Selective Androgen Receptor Modulator (SARM) Treatment Improves Muscle Strength and Body Composition, and Prevents Bone Loss in Orchidectomized Rats
Wenqing Gao, Peter J. Reiser, Christopher C. Coss, Mitch A. Phelps, Jeffrey D. Kearbey, Duane D. Miller, and James T. Dalton*
Division of Pharmaceutics, College of Pharmacy, ***artment of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43210; ***artment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163
* To whom correspondence should be addressed. E-mail: [email protected].
The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in our previous study (Endocrinology 145(12):5420-28, 2004). In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-tr***uoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 weeks. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT (3 mg/kg) treated animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights over 2-fold greater than that observed in intact controls, while S-4 (3 mg/kg) returned these androgenic organs to only 16% and 17%, respectively, of the control levels. S-4 (3, 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density (BMD) than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary, and significantly decreased plasma LH and FSH levels in castrated animals in a dose ***endent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.
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Originally Posted by Anthony Roberts
