Abstract
SARM‐2f a selective androgen receptor (AR) modulator, increases skeletal muscle mass and locomotor activity in rats. This study aimed to clarify its pharmacological effects in monkeys. In reporter assays, the EC50 values of SARM‐2f for rat, monkey, and human AR were 2.5, 3, and 3.6 nmol/L, respectively; those of testosterone were 12, 3.2, and 11 nmol/L, respectively. A single oral administration (10 mg/kg SARM‐2f) produced a maximal plasma concentration of 3011 ng/mL, with an area under the 24 hours concentration‐time curve of 8152 ng·h/mL in monkeys. Body weight (BW), lean body mass (LBM), and plasma levels of total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, lipoprotein (a), alanine aminotransferase, and asparagine aminotransferase were measured after 4 weeks of treatment with SARM‐2f (1, 3, and 10 mg/kg/day, QD, p.o.) or testosterone enanthate (TE; 2 mg/kg/2 weeks, s.c.) in monkeys. BW and LBM were significantly increased by 12% each by SARM‐2f at 10 mg/kg, and by 5% and 8%, respectively, by TE, but these effects were not statistically significant. Plasma levels of all lipids were either decreased or showed a tendency to be decreased by SARM‐2f. TE decreased the triglyceride level and increased the low‐density lipoprotein cholesterol level. Liver marker levels were not changed by either SARM‐2f or TE. Our data demonstrated that SARM‐2f exerted anabolic effects and produced a lipid profile that differed from that produced by testosterone in monkeys, suggesting that SARM‐2f might be useful for diseases such as sarcopenia.
Highlights
The androgen receptor (AR) activation of monkey AR was examined by reporter assays, the anabolic effects were assessed using body weight (BW) and lean body mass (LBM), and the potential cardiovascular or liver side effects were assessed by blood biochemistry tests
Sarcopenia is defined as an age-associated loss in skeletal muscle function and muscle mass
The recent treatment guidelines issued by the International Conference on Sarcopenia and Frailty Research strongly recommend the prescription of resistance-based physical activity, and
Summary
Age-related sarcopenia or cachexia is associated with a decrease in muscle mass and strength; this reduces the quality of life and increases nursing care requirements and mortality.[1,2,3] Sarcopenia and cachexia represent unmet needs, and the sarcopenia medical care guidelines were established recently.[4,5] Medication provides one treatment option, and the ghrelin agonist anamorelin was approved for this. Anamorelin increased body weight and muscle mass and improved anorexia in cancer cachexia.[6] anamorelin did not improve grip strength.[6] In contrast, testosterone can improve muscle strength.[7] there is a concern that long-term testosterone use may cause adverse cardiovascular events because of its impact on the blood lipid profile.[8,9,10] the development of alternative therapeutic agents is required. The androgen receptor (AR) activation of monkey AR was examined by reporter assays, the anabolic effects were assessed using body weight (BW) and lean body mass (LBM), and the potential cardiovascular or liver side effects were assessed by blood biochemistry tests. This study shows the anabolic effect of a SARM compound, SARM-2f, together with its favorable effect on the blood lipid profile in monkeys.
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