Ibudilast (AV-411)

  title={Ibudilast (AV-411)},
  author={Annemarie Ledeboer and Mark R Hutchinson and Linda R Watkins and Kirk W Johnson},
  journal={Expert Opinion on Investigational Drugs},
  pages={935 - 950}
The treatment of neuropathic pain is a major unresolved medical challenge. Present pharmacotherapies only have modest efficacy and numerous side effects. The use of opioid analgesics is additionally coupled with dependence and withdrawal syndromes. Ibudilast (AV-411) is a non-selective phosphodiesterase inhibitor that is also known to suppress glial cell activation. It has been used clinically for other indications with a good safety profile. As glial cell activation is considered to crucially… 

Anticytokine therapy in neuropathic pain management

Anticytokine agents currently on the market are effective for the treatment of mostly inflammatory pain conditions, and are starting to be introduced for neuropathic pain states; however, their use is limited by potential life-threatening complications.

Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease

Ibudilast is a relatively nonselective phosphodiesterase inhibitor which has been marketed for almost 20 years in Japan for treating asthma. More recently it has been found to have anti-inflammatory

Neuroimmune interactions and pain: focus on glial-modulating targets.

The role of glia in neuropathic pain and opioid administration is described, as well as the potential superior efficacy and wider therapeutic indices provided by drugs that modulate specific glial function via novel targets.

Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain

The failure of previously tested antioxidants, neuroprotective agents, anticonvulsants and antidepressants as therapeutic or preventative strategies are discussed, and individualized, mechanism-based therapeutic options for CIPNP associated with each of the three main drug groups are suggested.

Reviewand neuropathic pain - a review

The intricate link of TNF-α with other neuro-inflammatory signaling systems (e.g., chemokines and p38 MAPK) has indeed inspired a systems approach perspective for future drug development in treating neuropathic pain.


Identification of glial-mediated mechanism inducing opioid side effects includes cytokine receptor, κ-opioid receptor, NMDA receptor and toll like receptor (TLR), which is important in the complex syndrome of opioid dependence and withdrawal.

[Toll-like receptor 4: the potential therapeutic target for neuropathic pain].

The structure, function, and mechanism of Toll-like receptor 4 are reviewed as well as the development of TLR4-targeted drugs.

Opioids: a two-faced Janus

  • K. Ahlbeck
  • Medicine, Biology
    Current medical research and opinion
  • 2011
There remains a continuing need for innovative therapeutic strategies for the treatment of long-term pain, with the most promising alternatives appear to be the use of traditional opioids together with peripheral opioid antagonists, combining opioids with glial cell modulators, and theUse of novel agents with µ-receptor agonist and noradrenaline reuptake inhibitor activity within the same molecule (MOR-NRI compounds).

Review Opioids: a two-faced Janus

New analgesic therapies are needed that are associated with fewer adverse effects, whilst providing sustainable pain relief for patients with long-term pain.

Chronic Pain and Decreased Opioid Efficacy: An Inflammatory Link.




The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain.

The results indicate that AV411 is effective in diverse models of neuropathic pain and support further exploration of its potential as a therapeutic agent for the treatment of Neuropathic pain.

Gabapentin in the treatment of neuropathic pain

Gabapentin has antihyperalgesic and antiallodynic properties but does not have significant actions as an anti-nociceptive agent, and its mechanisms of action appear to be a complex synergy between increased GABA synthesis, non-NMDA receptor antagonism and binding to the α2δ subunit of voltage dependent calcium channels.

Glia: novel counter-regulators of opioid analgesia

Emerging trends in the pharmacotherapy of chronic pain

It is hoped that the decade of pain control and research will lead to an arsenal of effective and safe analgesics that will conquer the problem of chronic pain.

Neuropathic pain: symptoms, models, and mechanisms

The relationships between clinical symptoms and experimental models of peripheral neuropathic pain are described, and a framework for understanding the potential mechanisms that involve primary neuronal dysfunction as well as pathological changes in neuron‐glial signaling is provided.

Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall.

Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks.

Neuroimmune Activation and Neuroinflammation in Chronic Pain and Opioid Tolerance/Hyperalgesia

  • J. DeleoF. TangaV. Tawfik
  • Biology, Medicine
    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
  • 2004
The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.