期刊
EXPERT OPINION ON INVESTIGATIONAL DRUGS
卷 16, 期 7, 页码 935-950出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.16.7.935
关键词
analgesia; astroglia; cytokine; ibudilast; microglia; neuropathic pain; opioids; phosphodiesterase inhibitor; withdrawal
资金
- NIDA NIH HHS [DA015642] Funding Source: Medline
- NIDCR NIH HHS [DE017782] Funding Source: Medline
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. lbudilast (AV-411) is a non-selective phospho. diesterase 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.
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