Pharmacological effects of SA96 (bucillamine) and its metabolites as immunomodulating drugs--the disulfide structure of SA-96 metabolites plays a critical role in the pharmacological action of the drug.
SA96 (generic name, bucillamine) is a disease-modifying anti-rheumatoid arthritis (RA) drug with immunological effects. This compounds has two sulfhydryl groups in its molecule, and the differences and similarities between this drug and D-penicillamine, which is also a sulfhydryl group-containing anti-rheumatic drug, have frequently been discussed. To clarify the pharmacological differences between these two drugs, we examined the concentrations of the compounds and its metabolites in serum and synovial fluid, paying special attention to the metabolites of SA96 produced in vivo. SA96 was metabolized in a very short time to SA981 which is a disulfide compound formed by intramolecular binding of two sulfhydryl groups, and transferred to synovial fluid. In addition SA981 had significant suppressive effects on IL-6 and IL-8 production by synovial cells in vitro. These results demonstrate that SA96, which has two sulfhydryl groups, exhibits anti-rheumatic effects via a pharmacological action clearly different from that of D-penicillamine.
Matsuno
H
H
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan. matsuno@ms.toyama-mpu.ac.jp
Sugiyama
E
E
Muraguchi
A
A
Nezuka
T
T
Kubo
T
T
Matsuura
K
K
Tsuji
H
H
D000276:Adjuvants, Immunologic / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004220:Disulfides / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D004220:Disulfides; D015850:Interleukin-6; D016209:Interleukin-8; D010396:Penicillamine; D003545:Cysteine; C026535:bucillamine