Mirogabalin Chemical Properties

Boiling point:

357.5±15.0 °C(Predicted)

Density 

1.104±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMF:0.5(Max Conc. mg/mL);2.39(Max Conc. mM)
Ethanol:1.25(Max Conc. mg/mL);5.97(Max Conc. mM)
PBS (pH 7.2):0.5(Max Conc. mg/mL);2.39(Max Conc. mM)
Water:5.36(Max Conc. mg/mL);25.61(Max Conc. mM)

form 

A crystalline solid

pka

4.65±0.10(Predicted)

color 

Light yellow to light brown

InChI

InChI=1S/C12H19NO2/c1-2-8-3-9-5-12(7-13,6-11(14)15)10(9)4-8/h4,9-10H,2-3,5-7,13H2,1H3,(H,14,15)/t9-,10-,12-/m1/s1

InChIKey

FTBQORVNHOIASH-CKYFFXLPSA-N

SMILES

[C@]12([H])[C@]([H])([C@@](CN)(CC(O)=O)C1)C=C(CC)C2

Mirogabalin Usage And Synthesis

Description

Mirogabalin is a calcium channel blocker with analgesic effects. It binds to the α₂δ-1 and α₂δ-2 subunits of voltage-dependent Ca²⁺ channels. Mirogabalin has potent and sustained analgesic effects (ED₅₀ = 2.5 mg/kg) in rats with diabetes induced by streptozotocin (STZ; ). Mirogabalin does not inhibit activities associated with CNS adverse effects of analgesics, such as rotarod performance (ID₅₀ = 9.4 mg/kg) or locomotor activity (ID₅₀ = 43.9 mg/kg), at its effective dose. Formulations containing mirogabalin are in clinical trials for diabetic peripheral neuropathic pain.

Uses

Mirogabalin is a two alpha2delta ligand which is investigated for the treatment of peripheral neuropathic pain, postherpetic neuralgia and fibromyalgia, showing promising results in patients with diabetic peripheral neuropathy.

brand name

Mirogabalin (brand name Tarlige; developmental code name DS-5565) is a gabapentinoid medication developed by Daiichi Sankyo.

Side effects

The most typical clinical adverse reactions of mirogabalin were dizziness (7.6%) and somnolence (5.1%). However, the occurrence rate was lower than with pregabalin, whose adverse effects were reported to include somnolence, balance disorder, fatigue, and peripheral edema, with an occurrence rate of 8.0%, 4.0%, 4.0%, and 4.0%, respectively[1].

Synthesis

1. (1R,5S,6S)-[6-(tert-butoxycarbonylaminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetate (9.82 g, 23.7 mmol) was added to 100 mL of 4N hydrochloric acid-ethyl acetate solution. 2. The reaction mixture was stirred at room temperature for 1 hour. 3. After completion of the reaction, the solvent was removed by distillation under reduced pressure. 4. The residue was dissolved in dichloromethane. 5. 5. Triethylamine was added dropwise to the above solution and the resulting white powder was subsequently collected by filtration. 6. The collected powder was washed with dichloromethane and then dried to give 4.02 g of white powder. 7. Finally, the powder was washed with ethanol and ethyl acetate to afford the target compound 2-((1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl)acetic acid as a white powder (2.14 g, 43% yield).

Mode of action

Mirogabalin is an analog of the neurotransmitter, gamma-aminobutyric acid (GABA). It is a potent and specific ligand of the α2δ subunit of voltage-dependent Ca2+channels, which reduces calcium (Ca2+) influx and neurotransmission in dorsal root ganglia (DRGs), inhibiting neurotransmitter release in presynaptic neuron endings.

References

[1] Hui Tang. “The Clinical Application and Progress of Mirogabalin on Neuropathic Pain as a Novel Selective Gabapentinoids.” Mediators of Inflammation 2023 (2023): 4893436.