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Chemical Compound Review

Eyevinal     2-methyl-1-(8-propan-2-yl- 1,9...

Synonyms: Pinatos, ibudilast, Ibudilastum, Ketas, Lopac-I-0157, ...
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Disease relevance of Ke Tas


Psychiatry related information on Ke Tas

  • These results indicate a dose-dependent protective effect of ibudilast against cerebrovascular white matter lesions and suggest a potential use for ibudilast in the treatment of vascular dementia [5].

High impact information on Ke Tas


Chemical compound and disease context of Ke Tas


Biological context of Ke Tas

  • Similar to topical application, i.v. KC-404 (0.5 mg/kg) produced pial arteriolar dilation without significantly altering arterial blood pressure [9].
  • 2. Ibudilast was a non-selective inhibitor of partially purified cyclic nucleotide PDE isoenzymes from pig aorta and bovine tracheal smooth muscle, exhibiting only moderate potency against bovine tracheal PDE IV (IC50 = 12 +/- 4 microM, n = 3) [10].
  • These data also suggest that KC-404 produces cerebral vasodilation predominantly by potentiating prostanoid-mediated dilation [9].
  • Ibudilast at 10 - 100 microM significantly attenuated the H(2)O(2)-induced decrease in cell viability [11].
  • These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A [3].

Anatomical context of Ke Tas

  • These results suggest that ibudilast may be a useful neuroprotective and anti-dementia agent counteracting neurotoxicity in activated microglia [7].
  • The purpose of this study was to characterize the nature of the response to KC-404 in the cerebral microcirculation of the newborn pig [9].
  • Histologically, inflammatory cell infiltration in the lumbar spinal cord was significantly reduced in Ibudilast-treated animals as compared to control animals [2].
  • 5. Ibudilast had no effect on either GTP- or calcium-stimulated phosphatidylinositol specific-phospholipase C activity of lung membranes [12].
  • Ibudilast mildly suppressed MBP-induced proliferation of T cells in regional lymph nodes, the secretion of interferon-gamma from T cells activated by MBP in CFA, and the secretion of tumor necrosis factor-alpha from macrophages [2].

Associations of Ke Tas with other chemical compounds


Gene context of Ke Tas

  • Sensitive real-time PCR for quantifying cytokine mRNA in the blood CD4+ cells revealed that the ibudilast monotherapy significantly reduced tumour necrosis factor-alpha and interferon (IFN)-gamma mRNA and the IFN-gamma/interleukin-4 mRNA ratio, suggesting a shift in the cytokine profile from Th1 toward Th2 dominancy [15].
  • Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4 [16].
  • The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3 [16].
  • Ibudilast suppresses TNFalpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS [17].
  • Ibudilast may be a promising therapy for MS and its clinical effects warrant further study [15].

Analytical, diagnostic and therapeutic context of Ke Tas


  1. Anti-apoptotic effect of cGMP in cultured astrocytes: inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore. Takuma, K., Phuagphong, P., Lee, E., Mori, K., Baba, A., Matsuda, T. J. Biol. Chem. (2001) [Pubmed]
  2. Ibudilast, a phosphodiesterase inhibitor, ameliorates experimental autoimmune encephalomyelitis in Dark August rats. Fujimoto, T., Sakoda, S., Fujimura, H., Yanagihara, T. J. Neuroimmunol. (1999) [Pubmed]
  3. Effect of ibudilast, a novel antiasthmatic agent, on anaphylactic bronchoconstriction: predominant involvement of endogenous slow reacting substance of anaphylaxis. Ohashi, M., Uno, T., Nishino, K. Int. Arch. Allergy Immunol. (1993) [Pubmed]
  4. Ibudilast protects against neuronal damage induced by glutamate in cultured hippocampal neurons. Tominaga, Y., Nakamura, Y., Tsuji, K., Shibata, T., Kataoka, K. Clin. Exp. Pharmacol. Physiol. (1996) [Pubmed]
  5. Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat. Wakita, H., Tomimoto, H., Akiguchi, I., Lin, J.X., Ihara, M., Ohtani, R., Shibata, M. Brain Res. (2003) [Pubmed]
  6. Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line. Yoshioka, A., Yamaya, Y., Saiki, S., Kanemoto, M., Hirose, G., Pleasure, D. J. Neurochem. (2000) [Pubmed]
  7. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia. Mizuno, T., Kurotani, T., Komatsu, Y., Kawanokuchi, J., Kato, H., Mitsuma, N., Suzumura, A. Neuropharmacology (2004) [Pubmed]
  8. Pharmacological studies on newly synthesized anti-allergic agents, 2-methyl-3-piperidino-beta-propionaphtone hydrochloride (KZ-111) and 3-isobutyryl-2-isopropylpyrazole-[1, 5-a] pyridine (KC-404). Nagai, H., Iwamoto, T., Nishiyori, T., Takizawa, T., Tsuchiya, H., Koda, A. Jpn. J. Pharmacol. (1983) [Pubmed]
  9. The role of prostanoids in the mediation of responses to KC-404, a novel cerebrovasodilator. Armstead, W.M., Mirro, R., Leffler, C.W., Busija, D.W. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  10. Possible role of cyclic AMP phosphodiesterases in the actions of ibudilast on eosinophil thromboxane generation and airways smooth muscle tone. Souness, J.E., Villamil, M.E., Scott, L.C., Tomkinson, A., Giembycz, M.A., Raeburn, D. Br. J. Pharmacol. (1994) [Pubmed]
  11. Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model. Takuma, K., Lee, E., Enomoto, R., Mori, K., Baba, A., Matsuda, T. Br. J. Pharmacol. (2001) [Pubmed]
  12. Inhibition by ibudilast of leukotriene D4-induced formation of inositol phosphates in guinea-pig lung. Etoh, S., Ohashi, M., Baba, A., Iwata, H. Br. J. Pharmacol. (1990) [Pubmed]
  13. Inhibitory effect of ibudilast (KC-404) on the expression of the beta2 integrin family on an eosinophilic cell line (EoL-1). Chihara, J., Urayama, O., Kayaba, H., Honda, K., Saito, N., Hayashi, N., Kurachi, D., Yamamoto, T. Ann. Allergy Asthma Immunol. (1998) [Pubmed]
  14. Relaxation and potentiation of cGMP-mediated response by ibudilast in bovine tracheal smooth muscle. Nakahara, T., Yunoki, M., Moriuchi, H., Mitani, A., Sakamoto, K., Ishii, K. Naunyn Schmiedebergs Arch. Pharmacol. (2002) [Pubmed]
  15. Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis. Feng, J., Misu, T., Fujihara, K., Sakoda, S., Nakatsuji, Y., Fukaura, H., Kikuchi, S., Tashiro, K., Suzumura, A., Ishii, N., Sugamura, K., Nakashima, I., Itoyama, Y. Mult. Scler. (2004) [Pubmed]
  16. Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. Kishi, Y., Ohta, S., Kasuya, N., Sakita, S., Ashikaga, T., Isobe, M. Cardiovascular drug reviews. (2001) [Pubmed]
  17. Ibudilast suppresses TNFalpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS. Suzumura, A., Ito, A., Yoshikawa, M., Sawada, M. Brain Res. (1999) [Pubmed]
  18. Inhibitory effect of ibudilast on urinary albumin excretion in type 2 diabetes mellitus with microalbuminuria. Hoshino, T., Ikeda, T. Nephron (2002) [Pubmed]
  19. Pharmacological effects of ibudilast on cerebral circulation: a PET study. Fukuyama, H., Kimura, J., Yamaguchi, S., Yamauchi, H., Ogawa, M., Doi, T., Yonekura, Y., Konishi, J. Neurol. Res. (1993) [Pubmed]
  20. Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells. Rile, G., Yatomi, Y., Qi, R., Satoh, K., Ozaki, Y. Thromb. Res. (2001) [Pubmed]
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