Short-Term Outcomes of Mirogabalin in Patients with Peripheral Neuropathic Pain: A Retrospective Study

Background: Mirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin administration in patients with peripheral neuropathic pain who ceased treatment with pregabalin.Methods: We retrospectively assessed peripheral neuropathic pain using the neuropathic pain screening questionnaire (NeP score) in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had switched from pregabalin to mirogabalin due to lack of efficacy or adverse events. Differences in the treatment course (i.e., numeric rating scale (NRS) scores) were compared using one-way analysis of variance with Bonferroni post hoc tests.Results: The mean age of the patients was 72.3 years (range, 30–94 years), and the mean duration of disease was 37 months (range, 3–252 months). After treatment with mirogabalin for 1 week, NRS scores significantly decreased compared with baseline and continued to decrease over time. After 8 weeks, NRS scores improved by ³30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin.Conclusions: The results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain.

Short-Term Outcomes of Mirogabalin in Patients with Peripheral Neuropathic Pain: A Retrospective Study

Background: Mirogabalin, which is approved for the treatment of peripheral neuropathic pain in Japan, is a ligand for the α2δ subunit of voltage-gated calcium channels. Both pregabalin and mirogabalin act as nonselective ligands at the α2δ-1 and α2δ-2 subunits. Mirogabalin has a unique binding profile and long duration of action. Pregabalin has been reported to produce intolerable adverse effects in some patients. This study investigated outcomes associated with mirogabalin in patients with peripheral neuropathic pain who withdrew from treatment with pregabalin. Methods: We retrospectively assessed peripheral neuropathic pain in 187 patients (58 men, 129 women) who were treated with mirogabalin. All patients had been treated with pregabalin and withdrew from therapy due to lack of efficacy or adverse events. The mean age of patients was 72.3 years (range, 30–94 years), and mean duration of disease was 37 months (range, 3–252 months). Results: After treatment with mirogabalin for 1 week, numeric rating scale (NRS) scores decreased significantly compared with baseline, and continued to decrease over time . After 8 weeks, NRS scores improved by ³30% from baseline in 113 patients (69.3%). Twenty-four patients (12.8%) stopped mirogabalin treatment due to adverse events. Somnolence (26.7%), dizziness (12.3%), edema (5.9%), and weight gain (0.5%) were noted as adverse events of mirogabalin. Conclusions: The results of this investigation indicate that mirogabalin is safe and effective for reducing peripheral neuropathic pain.

Neuropeptide FF (FLFQPQRF-NH2) and its Fragments Bind to α2δ Subunit of Voltage-Gated Calcium Channels

Purpose: Gabapentin, a drug for neuropathic pain, exerts its therapeutic effect via inhibition of the a2d subunit of N-type Ca2+ channels. Thus, finding peptides that specifically displace gabapentin from its binding site may lead to the development of new drugs. Methods: Displacement of bound [3H]-gabapentin in membrane preparations of rat cerebral cortex and of human Cav2.2/β3/α2δ1 expressed in CHO cell line. Results: Neuropeptide FLFQPQRF-NH2 specifically displaced bound [3H]-gabapentin in membrane preparations from rats and CHO cells. Truncation of the C-terminus of FLFQPQRF-NH2 by three amino acid residues to produce FLFQP-NH2 improved the displacement of gabapentin. FLFQP-NH2 displaced bound [3H]-gabapentin with IC50 and Ki values of 2.7 µM and 1.7 µM, respectively. Deletion of two amino acid residues (FQ) in the middle of the FLFQP-NH2 sequence yielded FLP-NH2 that displaced bound [3H]-gabapentin with a lower affinity. IC50 and Ki values were 11.9 µM and 7.8 µM, respectively. Neutral binding cooperativity existed when of FLFQP-NH2, FLP- NH2 and gabapentin when incubated together. FLFQPQRF-NH2 but not FLFQP-NH2 displaced bound [3H]-gabapentin to membrane preparations of human Cav2.2/b3/a2d1 expressed in CHO cells. Conclusion: FLFQPQRF-NH2, FLFQP-NH2 and FLP-NH2 displace bound gabapentin in membrane preparations of rat cerebral cortex. Binding cooperativity was detected when GBP/FLFQP-NH2/FLP-NH2 were incubated together. These novel binding sites may provide new approaches to modulate L-type Ca2+ channels.