From the Guidelines
Newly discovered sodium channel blockers include several promising compounds being investigated for pain management and neurological disorders, such as Nav1.7 selective blockers like JNJ-63955918, GDC-0276/GDC-0310, and PF-05089771, which target specific voltage-gated sodium channel subtypes with greater precision than traditional agents. These newer agents aim to improve upon traditional sodium channel blockers like lidocaine and carbamazepine by offering greater selectivity for specific channel subtypes, potentially reducing side effects while maintaining therapeutic efficacy. Some of the key newly discovered sodium channel blockers include:
- Nav1.7 selective blockers like JNJ-63955918, GDC-0276/GDC-0310, and PF-05089771
- Vixotrigine (BIIB074) which has shown potential for treating trigeminal neuralgia and small fiber neuropathy in clinical trials 1
- Natural compounds such as ciguatoxin analogs and tetrodotoxin derivatives are also being explored for their sodium channel blocking properties. The development of these compounds represents an important advance in addressing conditions like chronic pain, epilepsy, and cardiac arrhythmias through more targeted modulation of sodium channel activity in affected tissues. According to recent studies, sodium channel blockers include lamotrigine, lacosamide, carbamazepine, oxcarbazepine, and valproic acid, with five medium-quality studies supporting their role in treating pain in diabetic peripheral neuropathy (DPN) 1. However, it's essential to consider the potential risks and benefits of these medications, as well as individual patient factors, when selecting a treatment for pain management. Ranolazine, a medication with relatively specific late sodium channel current blockade, has also shown potential for reducing ventricular tachycardia and ventricular fibrillation in patients with ischemic heart disease 1.
From the Research
Newly Discovered Sodium Channel Blockers
- Lacosamide is a newly discovered sodium channel blocker that selectively enhances the slow inactivation of voltage-gated sodium channels 2, 3, 4, 5.
- Eslicarbazepine acetate is another sodium channel blocker that acts at voltage-gated sodium channels, although the precise mechanism of action is unclear 3, 4.
- Rufinamide is a sodium channel blocker with an unclear mechanism of action, although it does block voltage-dependent sodium channels 3, 4.
- Other newly developed agents include retigabine (ezogabine), brivaracetam, perampanel, and ganaxolone, which have shown promise in the treatment of epilepsy 4.
Characteristics of Newly Discovered Sodium Channel Blockers
- Lacosamide has a favorable pharmacokinetic profile, with approximately 100% bioavailability, minimal protein binding, and few drug-drug interactions 2, 5.
- Eslicarbazepine acetate has efficacy for partial-onset seizures in three randomized, double-blind, placebo-controlled studies 4.
- Rufinamide has been shown to have efficacy for partial-onset, primary generalized tonic-clonic, tonic-atonic, absence and atypical absence seizures 4.
- Lacosamide is well tolerated, with the most common adverse events being dizziness, nausea, and vomiting 2, 5.
Switching to Newly Discovered Sodium Channel Blockers
- Switching from traditional sodium channel blockers to lacosamide is usually successful, with a high overall rate of successful switching (81.3%) 6.
- The success rate of switching to lacosamide is higher in patients with adverse effects or concerns about metabolic derangement on traditional sodium channel blockers 6.