Compounds containing free sulfhydryl groups (e.g., L-cysteine (1), cysteamine, D-penicillamine, N-acetyl-L-cysteine (2)) have been shown to protect against experimental drug-induced liver injury (e.g., acetaminophen (3) toxicity in mice), while N-acetyl-DL-penicillamine is ineffective. Since 2 is rapidly deacetylated by the liver (unlike acetylpenicillamine), it is hypothesized to act as a prodrug of 1. Thiazolidine-4-carboxylic acid (4), a cyclic cysteine derivative with a masked sulfhydryl group, protects against various toxicities but has toxicity issues (seizures in children/overdose) and requires metabolism to liberate 1. We postulate 2-substituted thiazolidine-4-carboxylic acids (chemically unstable, dissociate in protic solvents) protect without prior metabolic activation. Evidence shows 2(RS)-methylthiazolidine-4(R)-carboxylic acid (MTCA, 5) (a) liberates 1 nonenzymatically at physiological pH and temperature, (b) is less toxic than 4 or 1, and (c) is more effective than 4 in protecting mice against acetaminophen-induced liver necrosis. Phencyclidine (1), a commonly abused drug with acute and long-term neurotoxic effects, has metabolites including ring-hydroxylated ones, amino alcohol (7), and amino acid (8). Ring-opened metabolites form via a-C-hydroxylation to carbinolamine 5 (which ring opens to amino aldehyde 6, leading to 7 and 8). An unidentified metabolite binds irreversibly to microsomal protein. Metabolically generated carbinolamines ionize to electrophilic iminium ions (trapped with cyanide as a-aminonitriles). For phencyclidine, this yields iminium ion 9 and a-aminonitrile 10 (with potential reactivity for covalent binding). Incubating rabbit liver microsomes with phencyclidine, Na14CN, and an NADPH-generating system, we isolated the organic base fraction, detected a major radioactive zone via thin-layer chromatography, and confirmed via mass spectrometry a product consistent with a-aminonitrile 10 (pseudomolecular ion MH+ 242, corresponding to 10 minus one mole of HCN).