Mirogabalin: could it be the next generation gabapentin or pregabalin?

Area of Science:

• Pharmacology
• Neurology
• Pain Management

Background:

• Gabapentinoid anticonvulsants are standard treatments for neuropathic pain.
• Pregabalin followed gabapentin, offering improved pharmacokinetic properties.
• Carbamazepine is an alternative for trigeminal neuralgia.

Purpose of the Study:

• To evaluate mirogabalin besylate (DS-5565, Tarlige®) as a novel gabapentinoid for neuropathic pain.
• To compare mirogabalin's efficacy and safety profile with existing treatments like pregabalin and gabapentin.

Main Methods:

• Mirogabalin exhibits high affinity and slow dissociation from α2δ-1 subunits in the dorsal root ganglion (DRG) for sustained analgesia.
• Low affinity and rapid dissociation from α2δ-2 subunits in the cerebellum contribute to reduced central nervous system adverse drug reactions (ADRs).
• Pharmacokinetic parameters including time to maximum plasma concentration (Tmax < 1 hour), protein binding (<25%), and renal excretion were assessed.

Main Results:

• Mirogabalin demonstrates greater sustained analgesia compared to pregabalin and gabapentin.
• It exhibits a lower incidence of central nervous system-specific ADRs.
• Equianalgesic doses indicate 30 mg mirogabalin is equivalent to 600 mg pregabalin or >1,200 mg gabapentin.
• Recommended initial adult dose is 5 mg twice daily, titrating up to 15 mg.

Conclusions:

• Mirogabalin is a promising novel gabapentinoid anticonvulsant for neuropathic pain.
• It offers enhanced therapeutic effects by targeting the DRG.
• Its distinct binding profile suggests a favorable safety profile with reduced cerebellar ADRs.