Detail of "1916-08-1"

Reference

Thiopurine methyltransferase

Thiopurine methyltransferase. Aromatic thiol substrates and inhibition by benzoic acid derivatives. Woodson, Lee C.; Ames, Matthew M.; Selassie, Cynthia Dias; Hansch, Corwin; Weinshilboum, Richard M. (Dep. Pharmacol., Mayo Clin., Rochester, MN 55905, USA). Mol. Pharmacol., 24(3), 471-8 (English) 1983. CODEN: MOPMA3. ISSN: 0026-895X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 7 Thiopurine methyltransferase (TPMT) [67339-09-7] catalyzes the S-methylation of thiopurine and thiopyrimidine drugs. Each of a series of benzoic acid derivs. tested inhibited purified human kidney TPMT. Concns.Several reagents with their cas registry numbers 108-98-5 and 65-85-0 are used here. required to inhibit TPMT by 50% ranged from 20 mM for 3,4-dimethoxy-5-hydroxybenzoic acid [1916-08-1] to 2.1 mM for acetylsalicylic acid [50-78-2]. Inhibition was noncompetitive or mixed with respect to both S-adenosyl-L-methionine [29908-03-0], the Me donor for the enzyme, and 6-mercaptopurine [50-44-2], the Me acceptor substrate. Preliminary structure-activity relationship anal. demonstrated that the benzoic acid structure was important for inhibitory activity, and that inhibition was enhanced by the addn. of methoxy and/or phenolic hydroxyl groups to the ring. Quant. structure-activity relationship anal. performed with addnl. benzoic acid derivs. showed that inhibitory activity could be modeled well by an equation that induced the normal Hammett const. and a parameter, p', related to lipophilicity. Several nonheterocyclic arom. thiol compds., including thiophenol [108-98-5] and thiosalicylic acid [147-93-3], were discovered to be substrates for TPMT. Apparent Km consts. for some of these arom. thiol compds. were in the nanomolar range, several orders of magnitude lower than those of the thiopurines and thiopyrimidines previously thought to be the only substrates for TPMT. These observations suggested that "aryl thiol methyltransferase" might be a better name than "thiopurine methyltransferase" for this enzyme. Discovery of new classes of inhibitors and substrates for this important drug-metabolizing enzyme has implications for drug metab. research and for clin. medicine. .

The effect of certain drugs on amphetamine-induced stereotyped behavior and brain amphetamine levels in the rat

The effect of certain drugs on amphetamine-induced stereotyped behavior and brain amphetamine levels in the rat. Lal, Samarthji; Missala, Krystyna; Sourkes, Theodore L.; Feldmuller, Francois (Dep. Psychiatry Biochem., McGill Univ., Montreal, Que., Can.). Biol. Psychiatry, 9(1), 3-10 (English) 1974. CODEN: BIPCBF. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) The effects of various b-blockers, inhibitors of catechol-O-methyltransferase, and atropine sulfate [55-48-1] on amphetamine-induced stereotyped behavior (ASB) and brain amphetamine [300-62-9] levels were studied in the rat. Atropine, propranolol-HCl [318-98-9] and pyrogallol [87-66-1] all prolonged ASB. This prolongation was assocd. with a delayed disappearance of amphetamine-3H from the brain. Pronethalol-HCl [51-02-5], tropolone [533-75-5], and 3,4-dimethoxy-5-hydroxybenzoic acid [1916-08-1] had no effect on ASB.