Overview
Ibudilast is a non-selective phosphodiesterase (PDE) inhibitor (PDE3, 4, 10, 11) and macrophage migration inhibitory factor (MIF) inhibitor approved in Japan and South Korea since 1989 for asthma and post-stroke dizziness (as Ketas). In the US it is investigational (MN-166), with FDA Fast Track designation for progressive MS and ALS.
The pivotal SPRINT-MS phase 2 trial showed ibudilast significantly slowed brain atrophy in primary and secondary progressive MS over 96 weeks. Other trials have explored its anti-neuroinflammatory effects in ALS, methamphetamine and alcohol use disorder, opioid withdrawal, and chronic neuropathic pain.
Quick facts
- Mechanism
- Non-selective PDE inhibitor and macrophage migration inhibitory factor (MIF) antagonist; suppresses glial activation
- Primary use
- Progressive MS (investigational); ALS, addiction, and neuropathic pain research
- Evidence
- moderate
- FDA
- Not approved
- Route
- Oral
- Typical results
- Slowed brain atrophy in progressive MS (SPRINT-MS); reduced craving and alcohol use in trials; mixed ALS data
Chemical information
Ibudilast (C₁₄H₁₈N₂O) is a anti-inflammatory compound with a molecular weight of 230.31 g/mol. Its structural characteristics underpin its biological activity in anti-inflammatory and immune modulation.
How Ibudilast works
Ibudilast inhibits multiple PDE isoforms (3, 4, 10, 11), elevating cAMP and cGMP in glial cells and inhibiting pro-inflammatory cytokine release. It also antagonizes MIF and toll-like receptor 4 signaling on microglia, suppressing chronic neuroinflammation thought to drive progressive MS, ALS, and addiction-related neuroplasticity.
By suppressing activated microglia and astrocytes, ibudilast reduces production of TNF-α, IL-1β, IL-6, and nitric oxide while increasing IL-10 and neurotrophic factors (NGF, GDNF, NT-4). This anti-neuroinflammatory profile is the rationale for its use in progressive MS, where chronic compartmentalized inflammation drives axonal loss.
In addiction medicine, ibudilast attenuates the neuroinflammatory response to opioids, alcohol, and methamphetamine and reduces drug-induced reinstatement in animal models. Human trials show reduced craving and consumption in alcohol and methamphetamine use disorders.
- PDE3/4/10/11 inhibition: Elevates cAMP/cGMP in glia and immune cells
- MIF antagonism: Reduces macrophage-driven inflammation
- TLR4 modulation: Suppresses microglial activation by opioids and danger signals
- Neurotrophic support: Upregulates NGF, GDNF, NT-4
- Anti-platelet effect: Mild antiplatelet activity from PDE inhibition
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Oral bioavailability | ~75% | Good absorption with food |
| Tmax | 4–6 hours | Gradual onset |
| Half-life | ~19 hours | Once- or twice-daily dosing |
| Metabolism | Hepatic (CYP2C19, 3A4) | Potential interactions |
| CNS penetration | Good; crosses BBB | Required for neurological effects |
Dosing & administration
Ibudilast dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for Ibudilast is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Nausea and GI upset
- • Headache
- • Fatigue
- • Depression (in MS trials)
- • Loss of appetite
Serious / potential risks
- • Hepatic transaminase elevation
- • Worsening depression
- • Hypersensitivity reactions
- • Limited long-term safety data outside Japanese asthma use
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| CYP2C19 substrates (clopidogrel) | Possible altered metabolism | Monitor antiplatelet response |
| Other PDE inhibitors | Additive cAMP/cGMP elevation | Use cautiously |
| Antihypertensives | Mild vasodilation may potentiate effect | Monitor blood pressure |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
Ibudilast is a anti-inflammatory compound with research interest in neuroinflammation, pde inhibition, als, ms. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying anti-inflammatory and immune modulation
- • Individuals interested in neuroinflammation under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
Related compounds
Frequently asked questions
References
- [1] Fox RJ, Coffey CS, Conwit R, et al.. Phase 2 trial of ibudilast in progressive multiple sclerosis (SPRINT-MS). N Engl J Med (2018). doi: 10.1056/NEJMoa1803583 PMID: 30157388
- [2] Ray LA, Bujarski S, Shoptaw S, et al.. Development of the neuroimmune modulator ibudilast for the treatment of alcoholism: a randomized, placebo-controlled, human laboratory trial. Neuropsychopharmacology (2017). doi: 10.1038/npp.2017.10 PMID: 28091534
- [3] Heo Y, Zhang Y, Gao D, Miller VM, Lawrence DA.. Anti-neuroinflammatory effects of ibudilast. Int Immunopharmacol (2014). doi: 10.1016/j.intimp.2014.06.020 PMID: 24946099