Laws and Penalties: Concerns over growing illegal AAS abuse by teenagers, and many of the just discussed long-term effects, led Congress in 1991 to place the whole AAS class of drugs into Schedule III of the Controlled Substances Act (CSA). Under this legislation, AAS are defined as any drug or hormonal substance, chemically and pharmacologically related to T (other than estrogens, progestins, and corticosteroids) that promotes muscle growth. The possession or sale of AAS without a valid prescription is illegal. Since 1991, simple possession of illegally obtained AAS carry a maximum penalty of one year in prison and a minimum $1,000 fine if this is an individual’s first drug offense. The maximum penalty for trafficking (selling or possessing enough to be suspected of selling) is five years in prison and a fine of $250,000 if this is the individual’s first felony drug offense. If this is the second felony drug offense, the maximum period of imprisonment and the maximum fine both double. While the above listed penalties are for federal offenses, individual states have also implemented fines and penalties for illegal use of AAS. State executive offices have also recognized the seriousness of AAS abuse and other drugs of abuse in schools. For example, the State of Virginia enacted a law that will allow student drug testing as a legitimate school drug prevention program (48, 49).
Many abusers who inject anabolic steroids may use nonsterile injection techniques or share contaminated needles with other abusers. In addition, some steroid preparations are manufactured illegally under nonsterile conditions. These factors put abusers at risk for acquiring lifethreatening viral infections, such as HIV and hepatitis B and C. Abusers also can develop endocarditis, a bacterial infection that causes a potentially fatal inflammation of the inner lining of the heart. Bacterial infections also can cause pain and abscess formation at injection sites.
The effects of sulfaphenazole, 1, on typical activities catalyzed by human cytochromes P450 of the 1A, 3A, and 2C subfamilies expressed in yeast were studied. 1 acts as a strong, competitive inhibitor of CYP 2C9 (K(i) = +/- microM); it is much less potent toward CYP 2C8 and 2C18 (K(i) = 63 and 29 microM, respectively) and fails to inhibit CYP 1A1, 1A2, 3A4, and 2C19. From difference visible spectroscopy experiments using microsomes of yeast expressing various human P450s, 1 selectively interacts only with CYP 2C9 with the appearance of a peak at 429 nm as expected for the formation of a P450 Fe(III)-nitrogenous ligand complex (Ks = +/- microM). Comparative studies of the spectral interaction and inhibitory effects of twelve compounds related to 1 with CYP 2C9 showed that the aniline function of 1 is responsible for the formation of the iron-nitrogen bond of the 429 nm-absorbing complex and is necessary for the inhibitory effects of 1. The study of two new compounds synthesized during this work, in which the N-phenyl group of 1 was replaced with either an ethyl group or a 3,4-dichlorophenyl group, showed that the presence of an hydrophobic substituent at position 1 of the pyrazole function of 1 is required for a strong interaction with CYP 2C9. A model for the binding of 1 in the CYP 2C9 active site is proposed; that takes into account three major interactions that should be at the origin of the high-affinity and specific inhibitory effects of 1 toward CYP 2C9: (i) the binding of its nitrogen atom to CYP 2C9 iron, (ii) an ionic interaction of its SO2N- anionic site with a cationic residue of CYP 2C9, and (iii) an interaction of its N-phenyl group with an hydrophobic part of the protein active site.