Immunomodulatory effect of a newly synthesized compound, TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo [2,1-b]thiazole-2-carboxamide) on antibody production in vivo and delayed-type hypersensitivity in mice.
The immunopharmacological effects of a newly synthesized compound in vivo, TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thi azo le-2- carboxamide), on the anti-SRBC plaque-forming cell (PFC) response and delayed-type hypersensitivity (DTH) reaction were investigated. Oral administration of TOK-8801 (0.1-10 mg/kg) resulted in the suppression of the PFC responses to varying doses of antigen (5 x 10(6), 2 x 10(7), 1 x 10(8)) in C3H/He strain mice (7 W) which are high responders to SRBC antigen. On the other hand, the compound augmented the PFC response in aged mice (8-9 months) in which the PFC response was markedly depressed compared with that in young mice. In the experiment of the methylated human serum albumin-induced DTH reaction, TOK-8801 augmented the reaction in low responder (C57BL/6) mice by oral administrations of 0.1-1 mg/kg for 5 days from the sensitization, whereas suppressed the reaction in high responder (ICR) mice. These immunopharmacological actions of TOK-8801 were compared in dose and activity with those of lobenzarit and bucillamine. Thus, these results suggest that TOK-8801 may act as an immunomodulating agent and would be expected to be a useful agent for autoimmune diseases such as rheumatoid arthritis.
Shibata
K
K
Medicinal Research Laboratories, Toyo Jozo Co., Ltd, Shizuoka, Japan.
Kobayashi
T
T
Takayanagi
N
N
Fujiwara
M
M
Yamamoto
I
I
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012709:Serum Albumin / Q000276:immunology; D012756:Sheep / Q000097:blood; D013844:Thiazoles / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000941:Antigens; D007093:Imidazoles; D012709:Serum Albumin; D013844:Thiazoles; C062839:TOK 8801