Mirogabalin
[CAS# 1138245-13-2]

Identification

• Classification: API >> Other chemicals
• Name: Mirogabalin
• Synonyms: (1R,5S,6S)-6-(Aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-ene-6-acetic acid; A 200-0700; DS 5565
• Molecular Formula: C₁₂H₁₉NO₂
• Molecular Weight: 209.28
• CAS Registry Number: 1138245-13-2
• SMILES: CCC1=C[C@@H]2[C@H](C1)C[C@@]2(CC(=O)O)CN

Properties

• Solubility: Slightly soluble (1.6 g/L) (25 ºC), Calc.^*
• Density: 1.104±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Boiling point: 357.5±15.0 ºC 760 mmHg (Calc.)^*
• Flash point: 170.0±20.4 ºC (Calc.)^*
• Index of refraction: 1.527 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

Mirogabalin is a novel drug belonging to the gabapentinoid class, developed for the treatment of neuropathic pain. It was discovered through efforts to identify compounds with similar efficacy to pregabalin and gabapentin but with improved receptor binding properties and fewer side effects. Neuropathic pain, arising from damage or dysfunction in the nervous system, represents a major therapeutic challenge, and gabapentinoids have been important in providing symptomatic relief. However, tolerability issues, such as dizziness and somnolence, limited their clinical use and motivated the search for improved molecules, leading to the development of mirogabalin.

Mirogabalin was synthesized by researchers at Daiichi Sankyo and introduced in the early 2010s. Its pharmacological activity is based on high-affinity binding to the α₂δ subunits of voltage-gated calcium channels, which play a crucial role in modulating neurotransmitter release and neuronal excitability. Unlike pregabalin, mirogabalin shows distinct binding kinetics, with higher selectivity and slower dissociation from the α₂δ-1 subunit, which is predominantly involved in neuropathic pain pathways, while showing faster dissociation from the α₂δ-2 subunit, which has been linked to side effects such as dizziness and sedation. This pharmacological profile was designed to maintain analgesic efficacy while improving tolerability.

The drug was approved in Japan in 2019 under the trade name Tarlige for the treatment of peripheral neuropathic pain, including painful diabetic peripheral neuropathy and postherpetic neuralgia. These approvals marked the first new gabapentinoid to reach clinical use in more than a decade. Clinical trials demonstrated that mirogabalin effectively reduces neuropathic pain intensity and improves patient quality of life, with a safety profile generally comparable or superior to earlier gabapentinoids.

Beyond diabetic neuropathy and postherpetic neuralgia, mirogabalin has been evaluated for other neuropathic pain conditions such as fibromyalgia and central neuropathic pain due to spinal cord injury. While early studies suggested potential benefits, results have varied, and its approval has so far remained limited to peripheral neuropathic pain in Japan and some Asian countries. Research continues to explore its role in other chronic pain syndromes, but regulatory approval in Europe and North America has not yet been achieved.

In terms of safety, mirogabalin’s adverse effects include dizziness, somnolence, peripheral edema, and weight gain, similar to other gabapentinoids, but the incidence of these effects appears to be reduced due to its unique binding kinetics. Dose adjustments are recommended for patients with renal impairment, as the drug is primarily excreted unchanged via the kidneys.

The discovery and clinical application of mirogabalin represent an important step in refining the gabapentinoid class to improve the management of neuropathic pain. By enhancing receptor subtype selectivity and optimizing binding dynamics, researchers were able to design a drug that addresses some of the limitations of earlier therapies while retaining their core benefits. Its development highlights the continuing need for effective and well-tolerated treatments in neuropathic pain, an area of high unmet medical need.