Ibudilast

Drugbox
IUPAC_name = 2-methyl-1-(2-propan-2-ylpyrazolo [1,5-a] pyridin-3-yl)propan-1-one

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CAS_number = 50847-11-5
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PubChem = 3671
DrugBank =
C=14|H=18|N=2|O=1
molecular_weight = 230.31 g/mol
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Ibudilast (current development codes: AV-411 or MN-166) is an antiinflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE-4 subtype to the greatest extent, [Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K. Preferential inhibition of human phosphodiesterase 4 by ibudilast. "Life Sciences". 2006 May 1;78(23):2663-8.] but also showing significant inhibition of other PDE subtypes. [Suzumura A, Ito A, Yoshikawa M, Sawada M. Ibudilast suppresses TNFalpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS. "Brain Research". 1999 Aug 7;837(1-2):203-12.] [Gibson LC, Hastings SF, McPhee I, Clayton RA, Darroch CE, Mackenzie A, Mackenzie FL, Nagasawa M, Stevens PA, Mackenzie SJ. The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family. "European Journal of Pharmacology". 2006 May 24;538(1-3):39-42.]

Ibudilast has bronchodilator, vasodilator [Kishi Y, Ohta S, Kasuya N, Sakita S, Ashikaga T, Isobe M. Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. "Cardiovascular Drug Reviews". 2001 Fall;19(3):215-25.] and neuroprotective effects, [Mizuno T, Kurotani T, Komatsu Y, Kawanokuchi J, Kato H, Mitsuma N, Suzumura A. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia. "Neuropharmacology". 2004 Mar;46(3):404-11.] [Yoshioka M, Suda N, Mori K, Ueno K, Itoh Y, Togashi H, Matsumoto M. Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia. "Pharmacological Research". 2002 Apr;45(4):305-11.] and is mainly used in the treatment of asthma and stroke. [Wakita H, Tomimoto H, Akiguchi I, Lin JX, Ihara M, Ohtani R, Shibata M. Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat. "Brain Research". 2003 Nov 28;992(1):53-9.] It inhibits platelet aggregation, [Rile G, Yatomi Y, Qi R, Satoh K, Ozaki Y. Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells. "Thrombosis Research". 2001 May 1;102(3):239-46.] and may also be useful in the treatment of 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. Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis. "Multiple Sclerosis". 2004 Oct;10(5):494-8.]

Ibudilast crosses the blood-brain barrier and suppresses glial cell activation. This activity has been shown to make ibudilast useful in the treatment of neuropathic pain and it not only enhances analgesia produced by opioid drugs, but also reduces the development of tolerance. [Ledeboer A, Hutchinson MR, Watkins LR, Johnson KW. Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes. "Expert Opinion on Investigational Drugs". 2007 Jul;16(7):935-50.]

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