Ibudilast

• CAT Number: I003810
• CAS Number: 50847-11-5
• Molecular Formula: C₁₄H₁₈N₂O
• Molecular Weight: 230.311
• Purity: ≥95%
• Target: PDE
• Solubility: DMSO:28 mg/ml；100 mM in ethanol
• Storage: Store at -20°C
• InChI: 1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3
• InChIKey: ZJVFLBOZORBYFE-UHFFFAOYSA-N
• SMILES: CC(C)C1=NN(C=CC=C2)C2=C1C(C(C)C)=O

Ibudilast(KC-404;AV-411;MN-166) is a relatively nonselective phosphodiesterase inhibitor which has been marketed for treating asthma.Target: PDEIbudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). 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. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory actvity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks [1, 2]. Ibudilast (AV-411) is a non-selective phosphodiesterase inhibitor that is also known to suppress glial cell activation. Preclinical data indicate that ibudilast crosses the blood-brain barrier, is well tolerated, is active on oral administration, reduces glial activation and attenuates pain symptoms in diverse rat models of neuropathic pain. In addition, it enhances acute morphine analgesia and attenuates morphine tolerance and withdrawal. Thus ibudilast may improve opioid efficacy and is a promising therapeutic candidate for neuropathic pain, with a novel mechanism of action [3].

Reference

1:Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence. Metz VE, Jones JD, Manubay J, Sullivan MA, Mogali S, Segoshi A, Madera G, Johnson KW, Comer SD.Neuropsychopharmacology. 2017 May 10. doi: 10.1038/npp.2017.70. [Epub ahead of print] PMID: 28393896 2:Ibudilast: a non‑selective phosphodiesterase inhibitor in brain disorders. Schwenkgrub J, Zaremba M, Mirowska-Guzel D, Kurkowska-Jastrzębska I.Postepy Hig Med Dosw (Online). 2017 Mar 2;71(0):137-148. PMID: 28258674 Free Article3:Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial. Ray LA, Bujarski S, Shoptaw S, Roche DJ, Heinzerling K, Miotto K.Neuropsychopharmacology. 2017 Feb 8. doi: 10.1038/npp.2017.10. [Epub ahead of print] PMID: 28091532 4:A double-blind, randomized, placebo-controlled pilot trial to determine the efficacy and safety of ibudilast, a potential glial attenuator, in chronic migraine. Kwok YH, Swift JE, Gazerani P, Rolan P.J Pain Res. 2016 Oct 31;9:899-907. eCollection 2016. PMID: 27826212 Free PMC Article5:Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. Fox RJ, Coffey CS, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Conwit R, Naismith R, Ashokkumar A, Bermel R, Ecklund D, Koepp M, Long J, Natarajan S, Ramachandran S, Skaramagas T, Thornell B, Yankey J, Agius M, Bashir K, Cohen B, Coyle P, Delgado S, Dewitt D, Flores A, Giesser B, Goldman M, Jubelt B, Lava N, Lynch S, Miravalle A, Moses H, Ontaneda D, Perumal J, Racke M, Repovic P, Riley C, Severson C, Shinnar S, Suski V, Weinstock-Gutman B, Yadav V, Zabeti A.Contemp Clin Trials. 2016 Sep;50:166-77. doi: 10.1016/j.cct.2016.08.009. Epub 2016 Aug 10. PMID: 27521810 6:Ibudilast for the treatment of multiple sclerosis. Goodman AD, Gyang T, Smith AD 3rd.Expert Opin Investig Drugs. 2016 Oct;25(10):1231-7. doi: 10.1080/13543784.2016.1221924. Epub 2016 Aug 22. Review. PMID: 27501293 7:Ibudilast attenuates expression of behavioral sensitization to cocaine in male and female rats. Poland RS, Hahn YK, Knapp PE, Beardsley PM, Bowers MS.Neuropharmacology. 2016 Oct;109:281-92. doi: 10.1016/j.neuropharm.2016.06.024. Epub 2016 Jun 22. PMID: 27343385 8:Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. DeYoung DZ, Heinzerling KG, Swanson AN, Tsuang J, Furst BA, Yi Y, Wu YN, Moody DE, Andrenyak DM, Shoptaw SJ.J Clin Psychopharmacol. 2016 Aug;36(4):347-54. doi: 10.1097/JCP.0000000000000511. PMID: 27269956 9:The glial cell modulator ibudilast attenuates neuroinflammation and enhances retinal ganglion cell viability in glaucoma through protein kinase A signaling. Cueva Vargas JL, Belforte N, Di Polo A.Neurobiol Dis. 2016 Sep;93:156-71. doi: 10.1016/j.nbd.2016.05.002. Epub 2016 May 6. PMID: 27163643 10:Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study. Worley MJ, Heinzerling KG, Roche DJ, Shoptaw S.Drug Alcohol Depend. 2016 May 1;162:245-50. doi: 10.1016/j.drugalcdep.2016.02.036. Epub 2016 Mar 3. PMID: 26993372 Free PMC Article