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 in vivo and delayed-type hypersensitivity in mice

Article

Author: Noriyasu Takayanagi ; Toyokazu Kobayashi ; Kensuke Shibata ; Masami Fujiwara ; Itaru Yamamoto

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.

01 Jan 1989·The Japanese Journal of Pharmacology

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).

Article

Author: Noriyasu Takayanagi ; Kensuke Shibata ; Masami Fujiwara ; Kenji Matsunari ; Itaru Yamamoto

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.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	JP	-	-
Rheumatoid Arthritis	Phase 2	-	Kumiai Chemical Industry Co., Ltd.	-
Rheumatoid Arthritis	Discovery	-	Asahi Kasei Corp.	-

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