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).

FUJIWARA Masami, SHIBATA Kensuke, TAKAYANAGI Noriyasu, MATSUNARI Kenji, YAMAMOTO Itaru

doi:10.1254/jjp.51.549

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).

DOI PubMed

FUJIWARA Masami

Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
SHIBATA Kensuke

Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
TAKAYANAGI Noriyasu

Medicinal Research Laboratories, Toyo Jozo Co., Ltd.
MATSUNARI Kenji

Research and Development Department, Kumiai Chemical Industry Co., Ltd.
YAMAMOTO Itaru

Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University

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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]thiazole2-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^-4M. 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.