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

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Eric Y. Chen ◽  
Sascha S. Beutler ◽  
Alan D. Kaye ◽  
Amber N. Edinoff ◽  
Seyed-Hossein Khademi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Neurotransmitter Release ◽  
Safety Margin ◽  
Current Evidence ◽  
Multimodal Approach ◽  
Peripheral Neuropathic Pain ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Selective Ligand ◽  
Chronic Pain Conditions

: 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.

scholarly journals Mirogabalin—A Novel Selective Ligand for the α2δ Calcium Channel Subunit

2021 ◽  
Vol 14 (2) ◽  
pp. 112
Author(s):  
Renata Zajączkowska ◽  
Joanna Mika ◽  
Wojciech Leppert ◽  
Magdalena Kocot-Kępska ◽  
Małgorzata Malec-Milewska ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Significant Proportion ◽  
Safety Margin ◽  
Dissociation Rate ◽  
New Drugs ◽  
Peripheral Neuropathic Pain ◽  
Ligand Selectivity ◽  
Analgesic Effects ◽  
Pain Syndromes ◽  
Selective Ligand

The efficacy of neuropathic pain control remains unsatisfactory. Despite the availability of a variety of therapies, a significant proportion of patients suffer from poorly controlled pain of this kind. Consequently, new drugs and treatments are still being sought to remedy the situation. One such new drug is mirogabalin, a selective ligand for the α2δ subunits of voltage-gated calcium channels (VGCC) developed by Sankyo group for the management of neuropathic pain. In 2019 in Japan, mirogabalin was approved for peripheral neuropathic pain following the encouraging results of clinical trials conducted with diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) patients. The ligand selectivity of mirogabalin for α2δ-1 and α2δ-2 and its slower dissociation rate for α2δ-1 than for α2δ-2 subunits of VGCC may contribute to its strong analgesic effects, wide safety margin, and relatively lower incidence of adverse effects compared to pregabalin and gabapentin. This article discusses the mechanism of action of mirogabalin, presents data on its pharmacodynamics and pharmacokinetics, and reviews the available experimental and clinical studies that have assessed the efficacy and safety of the drug in the treatment of selected neuropathic pain syndromes.

scholarly journals The structural biology of voltage-gated calcium channel function and regulation

2006 ◽  
Vol 34 (5) ◽  
pp. 887-893 ◽  
Author(s):  
F. Van Petegem ◽  
D.L. Minor
Keyword(s):  
Neurotransmitter Release ◽  
Action Potentials ◽  
Molecular Switches ◽  
Voltage Gated ◽  
Calcium Dependent ◽  
Voltage Gated Calcium Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Soluble Calcium ◽  
Molecular Framework

Voltage-gated calcium channels (CaVs) are large (∼0.5 MDa), multisubunit, macromolecular machines that control calcium entry into cells in response to membrane potential changes. These molecular switches play pivotal roles in cardiac action potentials, neurotransmitter release, muscle contraction, calcium-dependent gene transcription and synaptic transmission. CaVs possess self-regulatory mechanisms that permit them to change their behaviour in response to activity, including voltage-dependent inactivation, calcium-dependent inactivation and calcium-dependent facilitation. These processes arise from the concerted action of different channel domains with CaV β-subunits and the soluble calcium sensor calmodulin. Until recently, nothing was known about the CaV structure at high resolution. Recent crystallographic work has revealed the first glimpses at the CaV molecular framework and set a new direction towards a detailed mechanistic understanding of CaV function.

Multimodal approach in postoperative peripheral neuropathic pain in dogs. Case report

2020 ◽  
Vol 3 ◽  
Author(s):  
Maira Rezende Formenton ◽  
Adriana Garcia ◽  
Denise T Fantoni ◽  
Marco A A Pereira
Keyword(s):  
Neuropathic Pain ◽  
Case Report ◽  
Multimodal Approach ◽  
Peripheral Neuropathic Pain

scholarly journals Functions of Presynaptic Voltage-gated Calcium Channels

Function ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Annette C Dolphin
Keyword(s):  
Calcium Channels ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Voltage Dependence ◽  
Kinetic Properties ◽  
Excitable Cells ◽  
Single Action ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Vesicular Release

Abstract Voltage-gated calcium channels are the principal conduits for depolarization-mediated Ca2+ entry into excitable cells. In this review, the biophysical properties of the relevant members of this family of channels, those that are present in presynaptic terminals, will be discussed in relation to their function in mediating neurotransmitter release. Voltage-gated calcium channels have properties that ensure they are specialized for particular roles, for example, differences in their activation voltage threshold, their various kinetic properties, and their voltage-dependence of inactivation. All these attributes play into the ability of the various voltage-gated calcium channels to participate in different patterns of presynaptic vesicular release. These include synaptic transmission resulting from single action potentials, and longer-term changes mediated by bursts or trains of action potentials, as well as release resulting from graded changes in membrane potential in specialized sensory synapses.

MiR-30b-5p attenuates oxaliplatin-induced peripheral neuropathic pain through the voltage-gated sodium channel Nav1.6 in rats

2019 ◽  
Vol 153 ◽  
pp. 111-120 ◽  
Author(s):  
Lei Li ◽  
Jinping Shao ◽  
Jiangshuan Wang ◽  
Yaping Liu ◽  
Yidan Zhang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Peripheral Neuropathic Pain ◽  
Voltage Gated
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