薬理と治療

Abstract

Objective　To investigate whether mirogabalin induces analgesia via the α2δ-1 or α2δ-2 subunit of the voltage-gated calcium channels. Methods　Mutant mice with α2δ-1（R217A; arginine-to-alanine mutation at amino acid 217） or α2δ-2（R282A; arginine-to-alanine mutation at amino acid 282）were generated and used with the littermate wild type mice. The mutations are known to decrease binding to gabapentinoids. The specific binding amount of［3H］-mirogabalin was measured in the cerebral cortex and cerebellum of the mice. The analgesic effect of mirogabalin was evaluated in the mice with neuropathic pain induced by partial sciatic nerve ligation. Results　The binding amount of mirogabalin in the cerebral cortex, where α2δ-1 is mainly distributed, was significantly less in the α2δ-1（R217A）, but not in the α2δ-2（R282A）mutant mice, compared with the wild type mice. On the other hand, the binding amount of mirogabalin in the erebellum, where α2δ-2 is mainly distributed, was significantly less in the α2δ-2 （R282A）, but not in the α2δ-1（R217A）mutant mice, compared with the wild type mice. The analgesic effect of mirogabalin disappeared in the α2δ-1 （R217A）mutant mice, but was observed in the α2δ-2（R282A）mutant mice at the same level as the wild type mice. Conclusions　These results suggest that the binding of mirogabalin to α2δ-1 may be necessary for its own analgesic effect.