[No Title Available]

Teixeira, Mauro Martins; Miotla, JM; Cooper, Nicola J.; Gristwood, RW; Hellewell, PG

doi:10.1590/s0074-02761997000800025

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…IBUD inhibits phosphodiesterase-4 (PDE4) and -10 (PDE10) and macrophage migration inhibitory factor (MMIF) (Johnson et al, 2014). As PDE4 and MMIF are critically involved in proinflammatory signaling (Calandra and Roger, 2003;Teixeira et al, 1997), and PDE10 negatively regulates neurotrophin expression (Giampà et al, 2010), the inhibition of these molecules by IBUD has been theorized to reduce neuroinflammation and promote neurotrophin expression (Johnson et al, 2014). In support, IBUD enhances neurotrophin expression, reduces proinflammatory cytokine release, and attenuates neuronal death (Mizuno et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial

Ray

Bujarski

Shoptaw

et al. 2017

Neuropsychopharmacol

104

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Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by ∼50%. To advance medication development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in nontreatment-seeking individuals with current (ie, past month) mild-to-severe AUD. This study tested the safety, tolerability, and initial human laboratory efficacy of IBUD (50 mg b.i.d.) on primary measures of subjective response to alcohol as well as secondary measures of cue- and stress-induced changes in craving and mood. Participants (N=24) completed two separate 7-day intensive outpatient protocols that included daily visits for medication administration and testing. Upon reaching a stable target dose of IBUD (or matched placebo), participants completed a stress-exposure session (day 5; PM), an alcohol cue-exposure session (day 6; AM), and an i.v. alcohol administration session (day 6; PM). Participants stayed overnight after the alcohol administration, and discharge occurred on day 7 of the protocol. Medication conditions were separated by a washout period that was ⩾7 days. IBUD was well tolerated; however, there were no medication effects on primary measures of subjective response to alcohol. IBUD was associated with mood improvements on the secondary measures of stress exposure and alcohol cue exposure, as well as reductions in tonic levels of craving. Exploratory analyses revealed that among individuals with higher depressive symptomatology, IBUD attenuated the stimulant and mood-altering effects of alcohol as compared with placebo. Together, these findings extend preclinical demonstrations of the potential utility of IBUD for the treatment of AUD and suggest that depressive symptomatology should be considered as a potential moderator of efficacy for pharmacotherapies with neuroimmune effects, such as IBUD.

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