Delayed-type skin allergic reaction in guinea pigs induced by anti-rheumatic compounds with sulfhydryl groups.
Delayed-type skin allergic (DTA) reactions induced by various sulfhydryl compounds were investigated. Sulfhydryl compounds investigated were bucillamine and D-penicillamine: antirheumatic agents, SA981: an intramolecular cyclic disulfide of bucillamine, tiopronin: a hepatoprotective and potent antirheumatic agent and captopril: antihypertensive and potent antirheumatic agent. Guinea pigs were sensitized on day 1 by subcutaneous injection and day 7 by subcutaneous and intramuscular injection of emulsions of these compounds (3 mg/animal) with Freund's complete adjuvant. Two weeks after the second sensitization, 0.3 mg/animal of each compound was intradermally challenged and the 24 hr DTA reaction was evaluated. A large number of sulfhydril compounds showed positive in the DTA reactions and the intensity of these reactions had a good correlation with the frequency of the skin rashes referred to by the adverse effects in clinical reports of anti-rheumatic drugs. It is suggested that guinea pig DTA reaction may provide a good screening way to find new sulfhydryl or disulfide compounds with low incidence of skin rash. A novel sulfhydryl compound N-(2,2-dimethyl-3-mercaptopropionyl)-L-cysteine (SA3441) and its intramolecular cyclic disulfide (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), which show no DTA activity in guinea pigs, were found using the above-mentioned DTA reaction.
Suda
H
H
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Okamoto
M
M
Fukumoto
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology / Q000633:toxicity; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004342:Drug Hypersensitivity / Q000209:etiology*; D006168:Guinea Pigs; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced*; D007120:Immunochemistry; D008297:Male; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013438:Sulfhydryl Compounds; D003545:Cysteine; C026535:bucillamine