Preferential inhibition of human phosphodiesterase 4 by ibudilast

Huang, Zheng; Liu, Susana; Zhang, Lei; Salem, Myriam; Greig, Gillian; Chan, Chi Chung; Natsumeda, Yutaka; Noguchi, Kazuhito

doi:10.1016/j.lfs.2005.10.026

Cited by 51 publications

(23 citation statements)

References 37 publications

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“…In experimental models of pain, either disruption of spinal glial activation or antagonism of substances released by activated glia either prevent or reverse pain hypersensitivity (Watkins and Maier, 2003). It is considered a relatively nonselective phosphodiesterase (PDE) inhibitor, although it inhibits PDE types 3, 4, 10 and 11 more potently Kishi et al, 2000;Gibson et al, 2006;Huang et al, 2006). 5a]pyridine]) is marketed in Asia to treat bronchial asthma and post-stroke dizziness, based on its anti-inflammatory and cerebral vaso-relaxant properties (Kishi et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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Controlling neuropathic pain is an unmet medical need and we set out to identify new therapeutic candidates. AV411 (ibudilast) is a relatively nonselective phosphodiesterase inhibitor that also suppresses glial-cell activation and can partition into the CNS. Recent data strongly implicate activated glial cells in the spinal cord in the development and maintenance of neuropathic pain. We hypothesized that AV411 might be effective in the treatment of neuropathic pain and, hence, tested whether it attenuates the mechanical allodynia induced in rats by chronic constriction injury (CCI) of the sciatic nerve, spinal nerve ligation (SNL) and the chemotherapeutic paclitaxel (Taxol). Twice-daily systemic administration of AV411 for multiple days resulted in a sustained attenuation of CCI-induced allodynia. Reversal of allodynia was of similar magnitude to that observed with gabapentin and enhanced efficacy was observed in combination. We further show that multi-day AV411 reduces SNL-induced allodynia, and reverses and prevents paclitaxel-induced allodynia. Also, AV411 cotreatment attenuates tolerance to morphine in nerve-injured rats. Safety pharmacology, pharmacokinetic and initial mechanistic analyses were also performed. Overall, 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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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“…Likewise, 100 nM of AV1013 and 1 μM of AV411 were sufficient to suppress MIF and TNF-α production and to inhibit p65 nuclear translocation. AV411 has a mean half-life of 19 h and inhibits PDE 3,4,10 and 11 at IC 50 s ranging from approximately 1 μM to 10 μM [13, 43]. AV441 displayed less neurotoxicity than AV1013 at equivalent concentrations, which might result from the proposed neuroprotective actions of inhibiting PDE [52].…”

Section: Discussionmentioning

confidence: 99%

Ibudilast (AV411), and its AV1013 analog, reduce HIV-1 replication and neuronal death induced by HIV-1 and morphine

El‐Hage

Rodriguez

Podhaizer

et al. 2014

Aids

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“…A study utilizing 15 min intermittent footshock and 1 mg/kg methamphetamine priming injection in different cohorts demonstrated that ibudilast significantly reduced reinstatement behavior in both tests [37]. The anti-reinstatement effects of ibudilast were presumably the result of its neuroregulatory actions, which include attenuation of glial activity, production of the growth factor GDNF and the inhibition of phosphodiesterase activity [145]. This compound has no known direct interactions with dopamine, glutamate, opioid, serotonin or cannabinoid receptors, or with dopamine or serotonin transporters [143], and thus represents a distinct target for managing the consequences of methamphetamine exposure on stress systems.…”

Section: Investigation Of the Anti-reinstatement Potential Of Specifimentioning

confidence: 99%

Investigating Methamphetamine Craving Using the Extinction-Reinstatement Model in the Rat

Kufahl¹,

Olive²

2012

J Addict Res Ther

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Summary Like all other drugs of abuse, the primary therapeutic objective for treating methamphetamine addiction research is the maintenance of abstinence and prevention of relapse to habitual drug-taking. Compounds with the potential to prevent relapse are often investigated in rats that are trained to self-administer intravenous methamphetamine, subjected to extinction training where responding is no longer reinforced, and then given tests for reinstatement of drug-seeking behavior triggered by methamphetamine injections or re-exposure to drug-paired cues. Experimental compounds are administered to the animals prior to the reinstatement tests to evaluate their potential for attenuating or preventing drug-seeking behavior. This article describes the common procedures of the extinction-reinstatement model in studies of this type, and identifies areas of discrepancy. This is followed by a comprehensive overview of the currently published anti-reinstatement effects of pharmacological compounds, classified by the most relevant neurological systems associated with these compounds. The article concludes with a brief discussion of how the study of anti-reinstatement effects can be expanded to further verify existing positive results or to find novel neurobiological targets.

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Preferential inhibition of human phosphodiesterase 4 by ibudilast

Cited by 51 publications

References 37 publications

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

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

Ibudilast (AV411), and its AV1013 analog, reduce HIV-1 replication and neuronal death induced by HIV-1 and morphine

Investigating Methamphetamine Craving Using the Extinction-Reinstatement Model in the Rat

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