Immunomodulatory activity of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thiazole-2- carboxamide).
The in vitro and in vivo effects of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b] thiazole-2-carboxamide) on immune responses were investigated in comparison with that of levamisole (LMS). TOK-8801 enhanced the anti-sheep red blood cells (SRBC) plaque forming cells (PFC) response and mitogen-induced proliferative responses in murine splenocytes and thymocytes in vitro at concentrations of 10(-7)-10(-5) M, while LMS augmented these responses at 10(-4) M. The stimulatory effect of TOK-8801 as well as LMS on the antibody production was eliminated by the removal of T cells. TOK-8801 (0.5 mg/kg, p.o.) suppressed the in vivo generation of anti-SRBC PFC in normal mice, but the compound restored the depressed antibody production in restraint-stress mice which was mainly caused by helper T cell defects. From these results, TOK-8801 was shown to have an immunomodulatory activity in the antibody production.
Fujiwara
M
M
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Shibata
K
K
Takayanagi
N
N
Matsunari
K
K
Yamamoto
I
I
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008934:Mitogens; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013315:Stress, Psychological / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007093:Imidazoles; D008934:Mitogens; D013844:Thiazoles; C062839:TOK 8801