Ibudilast (development codes: AV-411 or MN-166) is an
anti-inflammatory drug used mainly in Japan, which acts as a
phosphodiesterase inhibitor, inhibiting the
PDE4 subtype to the greatest extent,[1] but also showing significant inhibition of other PDE subtypes.[2][3]
Medical uses
In
Japan, ibudilast oral capsules are approved for the treatment of
asthma, and for improvement of
dizziness secondary to chronic cerebral circulation impairment associated with sequelae of
cerebral infarction.[4] Ibudilast ophthalmic solution is indicated for the treatment of
allergic conjunctivitis and
hay fever.[5]
It may have some use reducing methamphetamine,[6][7] opioid,[8] and alcohol[9] addiction.
Ibudilast is principally a PDE4 inhibitor but has also been shown to act as an
antagonist at the
toll-like receptor 4 (
TLR4).[17] This likely plays a large part in its effect, specifically its synergy with opioid drugs, its
anti-inflammatory effect, and its own
painkilling effect.[18] It is unknown if the PDE4-inhibiting properties
potentiate the effects of TLR4 inactivation and/or vice versa, despite that some of their effects are shared, such as
inflammation reducing properties.[19] TLR4 antagonists theoretically reverse the increase in pain and inflammation caused by most TLR4
agonists, which includes alcohol & many
opiate or
opioid drugs.[20]
References
^Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, et al. (May 2006). "Preferential inhibition of human phosphodiesterase 4 by ibudilast". Life Sciences. 78 (23): 2663–2668.
doi:
10.1016/j.lfs.2005.10.026.
PMID16313925.
^Suzumura A, Ito A, Yoshikawa M, Sawada M (August 1999). "Ibudilast suppresses TNFalpha production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS". Brain Research. 837 (1–2): 203–212.
doi:
10.1016/s0006-8993(99)01666-2.
PMID10434004.
S2CID7910607.
^Gibson LC, Hastings SF, McPhee I, Clayton RA, Darroch CE, Mackenzie A, et al. (May 2006). "The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family". European Journal of Pharmacology. 538 (1–3): 39–42.
doi:
10.1016/j.ejphar.2006.02.053.
PMID16674936.
^Kishi Y, Ohta S, Kasuya N, Sakita S, Ashikaga T, Isobe M (Fall 2001). "Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall". Cardiovascular Drug Reviews. 19 (3): 215–225.
doi:
10.1111/j.1527-3466.2001.tb00066.x.
PMID11607039.
^Mizuno T, Kurotani T, Komatsu Y, Kawanokuchi J, Kato H, Mitsuma N, Suzumura A (March 2004). "Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia". Neuropharmacology. 46 (3): 404–411.
doi:
10.1016/j.neuropharm.2003.09.009.
PMID14975696.
S2CID29284554.
^Yoshioka M, Suda N, Mori K, Ueno K, Itoh Y, Togashi H, Matsumoto M (April 2002). "Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia". Pharmacological Research. 45 (4): 305–311.
doi:
10.1006/phrs.2002.0949.
PMID12030794.
^Wakita H, Tomimoto H, Akiguchi I, Lin JX, Ihara M, Ohtani R, Shibata M (November 2003). "Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat". Brain Research. 992 (1): 53–59.
doi:
10.1016/j.brainres.2003.08.028.
PMID14604772.
S2CID24917936.
^Rile G, Yatomi Y, Qi R, Satoh K, Ozaki Y (May 2001). "Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells". Thrombosis Research. 102 (3): 239–246.
doi:
10.1016/s0049-3848(01)00258-4.
PMID11369417.
^Feng J, Misu T, Fujihara K, Sakoda S, Nakatsuji Y, Fukaura H, et al. (October 2004). "Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis". Multiple Sclerosis. 10 (5): 494–498.
doi:
10.1191/1352458504ms1070oa.
PMID15471363.
S2CID34072005.
^Ledeboer A, Hutchinson MR, Watkins LR, Johnson KW (July 2007). "Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes". Expert Opinion on Investigational Drugs. 16 (7): 935–950.
doi:
10.1517/13543784.16.7.935.
PMID17594181.
S2CID22321634.
^Jia ZJ, Wu FX, Huang QH, Liu JM (April 2012). "[Toll-like receptor 4: the potential therapeutic target for neuropathic pain]". Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. 34 (2): 168–173.
doi:
10.3881/j.issn.1000-503X.2012.02.013.
PMID22776604.
^Komatsu T, Sakurada S, Katsuyama S, Sanai K, Sakurada T (2009-01-01). "Mechanism of allodynia evoked by intrathecal morphine-3-glucuronide in mice". International Review of Neurobiology. 85: 207–219.
doi:
10.1016/S0074-7742(09)85016-2.
PMID19607972.