Acetothiolutamide is a selective androgen receptor modulator (SARM) derived from the nonsteroidal antiandrogen bicalutamide that was described in 2002 and was one of the first SARMs to be discovered and developed. It is a high- affinity, selective ligand of the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

(AR) (K_i = 2.1–4.9 nM), where it acts as a full agonist '' in vitro'', and has ''in vitro'' potency comparable to that of testosterone. However, '' in vivo'', acetothiolutamide displayed overall negligible androgenic effects, though significant (albeit very low) anabolic effects were observed at high doses. In addition, notable antiandrogen effects were observed in castrated male rats treated with testosterone propionate. The discrepancy between the ''in vitro'' and ''in vivo'' actions of acetothiolutamide was determined to be related to rapid plasma clearance and extensive hepatic metabolism into a variety of

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s with differing pharmacological activity, including AR partial agonism and

antagonism Antagonism may refer to: *The characteristic of an antagonist *Antagonism (chemistry), where the involvement of multiple agents reduces their overall effect *Receptor antagonist or pharmacological antagonist, a substance that binds to the site an ...

. In accordance with its poor

metabolic stability Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

, acetothiolutamide is not orally bioavailable, and shows activity only via injected routes such as

subcutaneous Subcutaneous may refer to: * Subcutaneous injection * Subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The ...

and

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

References

Acetanilides Nitriles Propionamides Selective androgen receptor modulators Thioethers Trifluoromethyl compounds {{genito-urinary-drug-stub

See also

References