Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes.

Abstract

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 contribute to neuropathic pain as well as opioid dependence and withdrawal, the authors conceived that ibudilast may be useful for treating these conditions. 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.

• Authors: Annemarie Ledeboer, Mark R Hutchinson, Linda R Watkins, Kirk W Johnson
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 16 Issue 7 Pg. 935-50 (Jul 2007) ISSN: 1744-7658 [Electronic] England
• PMID: 17594181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Drugs, Investigational
• Pyridines
• ibudilast

Topics

• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drugs, Investigational
• Female
• Follow-Up Studies
• Humans
• Male
• Neuralgia (diagnosis, drug therapy)
• Opioid-Related Disorders (drug therapy)
• Pain, Intractable (diagnosis, drug therapy)
• Prognosis
• Prospective Studies
• Pyridines (pharmacology, therapeutic use)
• Rats
• Substance Withdrawal Syndrome (drug therapy)
• Treatment Outcome