Isradipine

Evidence based treatments for smoking cessation have high recurrence rates. Targeting cue-induced craving, a strong predictor of smoking recurrence, may be critical to promoting sustained abstinence. We previously found that isradipine, an FDA-approved antihypertensive, enhanced the effect of virtual reality cue exposure therapy (VR-CET) on cue-induced craving. In this secondary analysis we tested whether this augmentation strategy was more beneficial for participants with high (relative to low) baseline cue-induced craving.

After a 24-h abstinence challenge, participants (N = 78) completed a single session of VR-CET with isradipine or placebo, and returned for a 24-h follow-up to repeat the procedure in a medication-free state. We conducted a moderator analysis to test the hypothesis that the effect of isradipine on cue-induced craving at follow-up would be larger among participants with higher (relative to lower) baseline cue-reactivity.

In the model of cue-induced craving at follow-up, the Group ×  Baseline cue-reactivity interaction was significant, p = .045. Among participants with higher baseline cue-induced craving, isradipine resulted in a large, significant reduction in mean craving in the follow-up session (M difference = -18.17, 95 % CI [-31.38, -4.95], p = .01, d = -1.46). Among participants with lower baseline cue-induced craving, results were not significantly different across groups (M difference = 1.38, 95 % CI [-12.98, 15.75], p = .85, d = 0.11).

Results suggest isradipine enhances VR-CET, particularly for individuals with higher baseline levels of cue-induced craving. Future studies testing prevention strategies that target higher cue-induced craving with isradipine to reduce rates of smoking recurrence are warranted.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease, primarily affecting the aging population. Despite the introduction of levodopa in the 1960s and significant progress in managing PD symptoms, no treatment has yet demonstrated neuroprotective efficacy. The complexity and multifactorial nature of PD continue to present substantial therapeutic challenges, prompting researchers to explore alternative approaches such as drug repurposing. This strategy offers a time- and cost-efficient route to drug development. Recent efforts have focused on repurposing agents originally developed for metabolic and other non-neurological disorders. Ongoing research is actively investigating several repurposed drugs originally intended for different conditions, including anti-hypertensives (isradipine, dexmedetomidine), anti-asthmatics (montelukast), phosphodiesterase5 inhibitors (sildenafil), antimicrobials (rifaximin), and various CNS-active agents (aripiprazole, escitalopram, paroxetine, venlafaxine, duloxetine, caffeine). While drug repurposing holds considerable promise, comprehensive preclinical and clinical studies are essential to validate these candidates for PD-specific therapeutic applications. This review aims to provide an in-depth overview of PD, encompassing its pathological and molecular characteristics, and to critically evaluate the current landscape of drug repurposing strategies to develop effective therapies for PD.