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

Kim, Jae Yeon; Abdi, Salahadin; Huh, Billy K.; Kim, Kyung Hoon

doi:10.3344/kjp.2021.34.1.4

Cited by 28 publications

(27 citation statements)

References 59 publications

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“…Note that the plasma concentration two hours after i.p. administration of 30 mg/kg to mice is 7.7 μg/mL 73 , which corresponds to 48 μM, and this exceeds the affinity of pregabalin for its primary targets alpha-2-delta-1 and alpha-2-delta-2 74 . Although reflexive pain-response alleviation after pregabalin administration was described in RIM3 rats 15 , 33 , 75 , the present study first describes the antihyperalgesic effect of pregabalin in the RIM6 and ASI model in the mouse, thus validating both models as suitable for use in pharmacological studies addressing the alleviation of sensory, nociplastic/FMS pain-related behaviors.…”

Section: Discussionmentioning

confidence: 93%

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5–6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.

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Section: Discussionmentioning

confidence: 93%

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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“…The side effects of this mechanism of action involve the central nervous system (CNS) primarily in the form of somnolence and dizziness. The CNS side effects might be related more to the α2δ-2 subunit, which is found mainly in the central nervous system (2,11). Mirogabalin has been shown to have longer dissociation half-lives against the α2δ-1 subunit when compared to the α2δ-2 subunit: 11.1 h (8.3 -16.4) versus 2.4 h (2.1 -2.8).…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

“…First approved in Japan in January 2019 for the treatment of peripheral neuropathic pain, mirogabalin is a ligand of the α2δ-1 and α2δ-2 subunits of VGCCs. Oral formulations are available in 2.5, 5, 10, and 15 mg tablets with a recommended starting dose of 5 mg twice daily (BID) with weekly increases by 5 mg up to a maximum dose of 15 mg BID ( 1 , 2 ). It hopes to join other first-line treatments for neuropathic pain like serotonin-noradrenaline reuptake inhibitors (duloxetine and venlafaxine), tricyclic antidepressants (amitriptyline, nortriptyline, desipramine, imipramine), and the other gabapentinoids (pregabalin, gabapentin) ( 3 ).…”

Section: Contextmentioning

confidence: 99%

“…Studies show that the analgesic effects may be related more to the α2δ-1 subunit, which is found in skeletal, smooth, and cardiac muscle, central and peripheral nervous systems, and endocrine tissues ( 2 ). One of the important advantages of mirogabalin over the other gabapentinoids is that it dissociates from the α2δ-1 subunit more slowly than gabapentin and pregabalin, resulting in greater potency and sustained analgesia ( 5 ).…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

“…This demonstrated that the binding affinity of mirogabalin for both α2δ-1 and α2δ-2 subunits is greater than that of pregabalin. Another advantage of mirogabalin is that it can achieve maximum plasma concentration in less than 1 hour, compared to the 1 hour it takes for pregabalin and 3 hours for gabapentin ( 2 , 10 ).…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

See 2 more Smart Citations

Mirogabalin as a Novel Gabapentinoid for the Treatment of Chronic Pain Conditions: An Analysis of Current Evidence

et al. 2021

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: Neuropathic pain has presented a challenge for physicians to treat and often requires a multimodal approach with both pharmacologic and lifestyle interventions. Mirogabalin, a potent, selective ligand of the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs), provides analgesia by inhibiting neurotransmitter release at the presynaptic end of the neuron. Mirogabalin offers more sustained analgesia than its gabapentinoid counterparts in addition to a wider safety margin for adverse events. Recent clinical trials of mirogabalin have demonstrated both efficacy and tolerability of the drug for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia, leading to its approval in Japan. While still not yet FDA approved, mirogabalin is still in its infancy and offers potential into the treatment of neuropathic pain and its associated comorbidities.

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