Ibudilast is a small molecule compound that functions as a phosphodiesterase inhibitor, exhibiting both anti-inflammatory and neuroprotective properties. It has a history of use in Japan and other Asian countries for specific conditions, and its broader therapeutic applications are being investigated globally.
Understanding Ibudilast’s Actions
Ibudilast exerts its effects by inhibiting phosphodiesterase (PDE) enzymes, particularly PDE4 and PDE10. By blocking these enzymes, ibudilast prevents the breakdown of cyclic AMP (cAMP) and cyclic GMP (cGMP), important signaling molecules. Increased levels of these cyclic nucleotides contribute to its anti-inflammatory and neuroprotective actions in the central nervous system.
Beyond PDE inhibition, ibudilast also modulates the activity of glial cells, such as microglia and astrocytes. Overactivation of these cells can lead to chronic inflammation and damage to neurons. Ibudilast helps to reduce this neuroinflammation and supports the survival of neurons. It also inhibits macrophage migration inhibitory factor (MIF) and toll-like receptor 4 (TLR4), further contributing to its anti-inflammatory effects.
Ibudilast’s ability to cross the blood-brain barrier is an advantage for treating disorders of the central nervous system. This allows it to directly influence brain and spinal cord processes. Additionally, ibudilast enhances the production of neurotrophic factors, proteins that support the growth and survival of neurons.
Current and Developing Therapeutic Roles
Ibudilast is approved in Japan, marketed as Ketas, for treating bronchial asthma, improving dizziness following a stroke, and for allergic conjunctivitis. In other parts of the world, ibudilast is primarily an investigational drug, undergoing clinical trials for several neurological conditions.
One area of investigation is Multiple Sclerosis (MS), particularly its progressive forms. In the SPRINT-MS Phase 2b clinical trial, ibudilast significantly slowed brain volume loss by 48% over nearly two years in patients with primary progressive MS or secondary progressive MS, compared to a placebo. This reduction in brain atrophy suggests a potential to slow disease progression.
Ibudilast is also being explored for its effects on neuropathic pain. Research in animal models has shown its effectiveness in preventing and reducing chronic neuropathic pain, including that caused by chemotherapy. Its mechanism involves attenuating activated glial cells, which are thought to contribute to persistent pain states.
Ibudilast is also under investigation for its role in substance use disorders, including opioid and methamphetamine addiction, and alcohol use disorder. Preclinical studies indicate that ibudilast may help reduce withdrawal symptoms and drug-seeking behaviors in animal models of addiction. While a recent clinical trial for alcohol use disorder did not show overall superiority to placebo, it suggested a positive effect in women.
Guidance for Patients
Ibudilast is a prescription medication, and its use requires medical supervision. It is not widely approved in many Western countries and is primarily accessible through participation in clinical trials or specific compassionate use programs. Patients considering or learning about this compound should always consult with a healthcare professional.
When taking ibudilast, some common side effects may occur. These can include gastrointestinal symptoms like nausea, diarrhea, and abdominal pain. Other reported side effects include headaches, dizziness, and fatigue. Less commonly, skin reactions or mood changes such as depression have been noted. It is important to discuss any side effects with a healthcare provider to manage them appropriately.