Total 3nb Phthalides
Also known as: 3NB, NBP, Dl-3-n-butylphthalide, 3-n-butylphthalide
Overview
3-n-butylphthalide (3NB), also known as Dl-3-n-butylphthalide, is a lipophilic phthalide derivative that can be naturally derived from celery seed (Apium graveolens) or synthesized. It is primarily investigated and used as a neuroprotective agent and a vascular and neurological supplement, often classified under phytochemicals or nutraceuticals. 3NB is well-known for its ability to cross the blood-brain barrier, allowing it to modulate neurological and vascular functions within the central nervous system. Its main applications are in the treatment and management of neurological and cerebrovascular conditions, particularly ischemic stroke and cerebral hemorrhage. Research indicates its potential to improve cerebral blood flow, reduce neurological deficits, and offer neuroprotection. The compound's efficacy and safety profile have been supported by multiple randomized controlled trials and recent systematic reviews and meta-analyses, indicating a moderate to advanced level of research maturity.
Benefits
3NB offers significant benefits primarily in patients with cerebral hemorrhage and ischemic stroke. A 2024 systematic review and meta-analysis of 19 randomized controlled trials demonstrated that Dl-3-n-butylphthalide significantly improved the clinical efficacy rate in cerebral hemorrhage patients, with a Risk Ratio (RR) of 1.25 (95% CI 1.19–1.31; p=0.00). This indicates a 25% higher chance of clinical improvement compared to control groups. The same review reported a significant enhancement in quality of life, with a Mean Difference (MD) of 13.93 (95% CI 11.88–15.98; p=0.000), suggesting a substantial positive impact on patient well-being. Additionally, 3NB was found to increase cerebral blood flow and velocity, reduce cerebral edema volume, and decrease homocysteine (Hcy) concentration, all contributing to improved neurological outcomes. The studies consistently showed no significant adverse reactions (RR = 0.68; 95% CI 0.39–1.18; p=0.10), highlighting a favorable safety profile. These benefits are particularly relevant for individuals in the acute and subacute phases of cerebral injury, with moderate to strong clinical effects and high statistical significance.
How it works
3NB exerts its therapeutic effects through multiple biological pathways, primarily by improving microcirculation and cerebral hemodynamics. It reduces oxidative stress by protecting mitochondrial function in neural cells and inhibiting platelet aggregation, which helps prevent clot formation and improve blood flow. Furthermore, 3NB plays a role in reducing neuroinflammation, thereby protecting against ischemic neuronal damage. Its lipophilic nature allows for good oral bioavailability and efficient crossing of the blood-brain barrier, enabling direct action within the central nervous system. The compound interacts with endothelial cells and neuronal mitochondria, modulating pathways involved in oxidative stress and inflammation to support brain health and recovery following injury.
Side effects
3NB is generally well tolerated, with clinical trials and meta-analyses reporting no significant adverse effects at therapeutic doses. The 2024 systematic review and meta-analysis found no significant increase in adverse reactions compared to control groups. While major side effects are not commonly reported, minor gastrointestinal discomfort or rare allergic reactions may occur, though these are uncommon (1-5% frequency). Serious adverse events directly linked to 3NB have not been reported in high-quality trials. Limited data exist regarding drug interactions; however, caution is advised when 3NB is combined with anticoagulants or antiplatelet agents due to potential additive effects on blood thinning. Contraindications are not well established, and its use in pregnant or lactating individuals has not been sufficiently studied, thus caution is recommended for these populations. Most safety data are derived from adult stroke patients, and information for pediatric populations is lacking.
Dosage
Clinical trials typically utilize 3NB at daily dosages ranging from 100 mg to 200 mg. The optimal dosage range is commonly 100-200 mg per day, administered orally, often in divided doses. There is no clearly established maximum safe dose, but doses up to 200 mg/day have been well tolerated in studies. For maximal benefit, 3NB is typically administered during the acute or subacute phases of stroke or cerebral hemorrhage. It is commonly available in oral capsule or tablet forms, though intravenous formulations also exist. While specific absorption factors are not extensively detailed, it is generally recommended to take 3NB with meals to potentially aid absorption. No specific cofactors are identified as necessary for its efficacy. Long-term safety data are limited, with current evidence supporting short to medium-term use.
FAQs
Is 3NB safe for long-term use?
Current evidence supports the safety of 3NB for short to medium-term use, particularly in acute and subacute phases of neurological conditions. However, long-term safety data are limited, and more research is needed for definitive conclusions.
Can 3NB be used for general cognitive enhancement?
Evidence for 3NB's benefits is primarily focused on cerebrovascular conditions like stroke and cerebral hemorrhage. There is currently no strong data to support its use for general cognitive enhancement in healthy individuals.
How quickly does 3NB work?
Clinical improvements with 3NB are typically observed within days to weeks of administration, particularly in patients recovering from stroke or cerebral hemorrhage, as noted in various clinical trials.
Are there any known drug interactions?
While data are limited, caution is advised when combining 3NB with blood thinners (anticoagulants or antiplatelet agents) due to the potential for additive effects on blood thinning. Consult a healthcare professional before combining medications.
Is 3NB effective for all types of stroke?
Most of the robust evidence supports 3NB's effectiveness in ischemic and hemorrhagic stroke. Its efficacy in other less common neurological conditions is not as extensively studied or supported by current research.
Research Sources
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1360932/full – This 2024 systematic review and meta-analysis of 19 RCTs (n≥30 per group) found that Dl-3-n-butylphthalide significantly improved clinical efficacy rate (RR=1.25), enhanced quality of life (MD=13.93), and improved cerebral blood flow parameters in cerebral hemorrhage patients. The study also reported no significant adverse reactions, indicating a favorable safety profile for 3NB in this population.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8453372/ – This systematic review focused on phthalate exposure risks and neurodevelopmental outcomes, highlighting the potential adverse effects of environmental phthalates. It is important to note that this research distinguishes between toxic environmental phthalates and the therapeutic phthalide compound 3NB, which has a different chemical structure and application.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11342836/ – This umbrella review examined the health effects of plastic-associated chemicals, including phthalates. While it discussed the need for careful evaluation of phthalate compounds due to potential adverse effects in environmental contexts, it also implicitly underscores the importance of distinguishing between environmental exposures and the targeted therapeutic use of specific phthalide derivatives like 3NB.
