IMMUNOMODULATING AND ARTICULAR PROTECTING ACTIVITIES OF A NEW ANTIRHEUMATIC DRUG, TAK-603

We investigated the pharmacological activities of a newly synthesized anti-rheumatic drug, TAK-603. (I) In vivo: In adjuvant arthritic (AA) rats, TAK-603 inhibited the hind paw swelling and the body weight loss , The minimum effective dose was 3.13 mg/kg/day (p.o.). Histological a nd radiographic studies showed that TAK-603 suppressed the development of synovial lesions and joint and bone destruction. TAK-603 was also effective in AA rats when administered for the first 7 days after the adjuvant injection. It suppressed type IV allergy (25 mg/kg/day, p.o.) but had no effect on type III allergy, It had little effect in acute inflammation, analgesic and antipyretic models. These data suggest tha t TAK-603 acts on the immune system, especially on cellular immunity. (2) In vitro: TAK-603 suppressed the mitogen-induced proliferation of mouse lymphocytes and the ConA-induced IFN-gamma and IL-2 production b y rat lymphocytes at 10(-7) to 10(-5) M. It also significantly inhibit ed the IL-1 induced extracellular matrix reduction in rabbit chondrocy tes. It had no effects on prostaglandin E(2) (PGE(2)) production in ra t peritoneal cells. These data show that TAK-603 has the ability to su ppress the immune system and protect cartilage from destruction. TAK-6 03 is expected to be a promising drug for rheumatoid arthritis.