Tetrahydrogestrinone (THG), known by the nickname The Clear, is a synthetic and orally active anabolic–androgenic steroid (AAS) which was never marketed for medical use. Tetrahydrogestrinone was developed completely in secret by Arnold as a designer drug, on the basis that doping testers would be unlikely to detect a totally new compound. Arnold developed a chemical similar to two obscure steroids marketed by BALCO, norbolethone and desoxymethyltestosterone, which had been reported in scientific literature but never entered mass production, and the banned anabolic steroids trenbolone and gestrinone, the latter of which was used to synthesize it.
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Tetrahydrogestrinone is a highly potent agonist of the androgen and progesterone receptors, around 10 times more potent than the comparison drugs nandrolone or trenbolone, but with no estrogenic activity. It has been found to bind to the androgen receptor with similar affinity to dihydrotestosterone and produces growth of muscle tissue. According to Patrick Arnold, due to the drug’s potency, he never had to supply significant quantities to BALCO, because “just a couple of drops under the tongue” were a sufficient dose.
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When Tetrahydrogestrinone reaches the nucleus of a cell, it binds to the androgen receptor at the ligand-binding pocket. Here it changes the expression of a variety of genes, turning on several anabolic and androgenic functions. It is the ligand‘s structure which determines the number of interactions that can take place with the human androgen receptor ligand-binding domain. Even minor modifications in the ligand’s structure have a great impact on the strength of the interactions this ligand has with the androgen receptor. THG, possessing a high affinity, establishes more van der Waals contacts with the receptor than with many other steroids. It is this higher affinity and specific geometry of Tetrahydrogestrinone which makes these interactions with the androgen receptor so strong, resulting in THG’s potency.
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Tetrahydrogestrinone, also known as 17α-ethyl-18-methyl-δ9,11-19-nortestosterone or as 17α-ethyl-18-methylestra-4,9,11-trien-17β-ol-3-one, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone (19-nortestosterone). It is a modification of gestrinone (17α-ethynyl-18-methyl-19-nor-δ9,11-testosterone) in which the ethynyl group has been hydrogenated into an ethyl group, thereby converting the steroid from a norethisterone (17α-ethynyl-19-nortestosterone) derivative with weak AR activity into a norethandrolone (17α-ethyl-19-nortestosterone) derivative with powerful AR activity. THG is closely related to RU-2309 (the 17α-methyl variant), trenbolone (δ9,11-19-nortestosterone), metribolone (17α-methyl-δ9,11-19-nortestosterone), and norboletone (17α-ethyl-18-methyl-19-nortestosterone).