Immunomodulating and articular protecting activities of a new anti-rheumatic drug, TAK-603.
We investigated the pharmacological activities of a newly synthesized anti-rheumatic drug, TAK-603. (1) 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 and 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 that 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 by rat lymphocytes at 10(-7) to 10(-5) M. It also significantly inhibited the IL-1 induced extracellular matrix reduction in rabbit chondrocytes. It had no effects on prostaglandin E2 (PGE2) production in rat peritoneal cells. These data show that TAK-603 has the ability to suppress the immune system and protect cartilage from destruction. TAK-603 is expected to be a promising drug for rheumatoid arthritis.
Ohta
Y
Y
Pharmaceutical Research Laboratories I, Osaka, Japan.
Fukuda
S
S
Baba
A
A
Nagai
H
H
Tsukuda
R
R
Sohda
T
T
Makino
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D001327:Autoimmune Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D002356:Cartilage / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D018501:Antirheumatic Agents; D016207:Cytokines; D007375:Interleukin-1; D011804:Quinolines; D014230:Triazoles; D015232:Dinoprostone; C104411:TAK 603