ʻAʻole ʻo Pregabalin kahi GABAA a i ʻole GABAB receptor agonist.
ʻO Pregabalin kahi gabapentinoid a hana ma ke kāohi ʻana i kekahi mau kahawai calcium.He ligand ia o ka pūnaewele subunit α2δ kōkua o kekahi mau kahawai calcium e hilinaʻi ana i ka volta (VDCCs), a no laila ke hana nei ma ke ʻano he mea hoʻopale o nā VDCC me nā subunit α2δ.ʻElua mau subunits α2δ hoʻopaʻa lāʻau, α2δ-1 a me α2δ-2, a hōʻike ka pregabalin i ka pili like no (a no laila ka nele o ka koho ma waena) o kēia mau pūnaewele ʻelua.Ua koho ʻo Pregabalin i kona hoʻopaʻa ʻana i ka subunit α2δ VDCC.ʻOiai ʻo ka pregabalin kahi analogue GABA, ʻaʻole ia e hoʻopaʻa i nā mea hoʻokipa GABA, ʻaʻole ia e hoʻololi i GABA a i ʻole GABA receptor agonist i loko o vivo, a ʻaʻole ia e hoʻololi pololei i ka transport GABA a i ʻole ka metabolism.Eia nō naʻe, ua ʻike ʻia ka pregabalin e hoʻonui i ka nui o ka nui o ka lolo o ka L-glutamic acid decarboxylase (GAD), ka enzyme kuleana no ka synthesizing GABA, a no laila e loaʻa paha kekahi mau hopena GABAergic indirect ma o ka hoʻonui ʻana i nā pae GABA i ka lolo.ʻAʻohe mea hōʻike i kēia manawa e hoʻopili ʻia nā hopena o pregabalin e kekahi ʻano hana ʻē aʻe ma mua o ka pale ʻana i nā VDCC me ka α2δ.E like me ka hoʻopaʻa ʻana i nā VDCC me ka α2δ-1 e pregabalin, ʻike ʻia ke kuleana no kāna mau hopena anticonvulsant, analgesic, a me anxiolytic.
ʻO ka endogenous α-amino acids L-leucine a me L-isoleucine, e like loa me ka pregabalin a me nā gabapentinoids ʻē aʻe i loko o ka hoʻolālā kemika, he mau ligand ʻike ʻia o ka subunit α2δ VDCC me ka pili like me nā gabapentinoids (eg, IC50 = 71 nM no L- isoleucine), a aia i loko o ka wai cerebrospinal kanaka ma micromolar concentrations (eg, 12.9 μM no L-leucine, 4.8 μM no L-isoleucine).Ua manaʻo ʻia ʻo ia paha nā ligands endogenous o ka subunit a hiki iā lākou ke hoʻokūkū kūʻē i nā hopena o gabapentinids.E like me ka gabapentinids like pregabalin a me gabapentin loaʻa nā nanomolar affinities no ka α2δ subunit, ko lākou potencies in vivo aia i loko o ka micromolar range haʻahaʻa, a ua ʻōlelo ʻia ka hoʻokūkū no ka hoʻopaʻa ʻana e nā waikawa L-amino endogenous ke kuleana no kēia ʻokoʻa.

Ua ʻike ʻia ʻo Pregabalin e loaʻa iā 6-fold ka pilina kiʻekiʻe ma mua o ka gabapentin no α2δ subunit-containing VDCCs i hoʻokahi haʻawina.Eia naʻe, ua ʻike ʻia kekahi noiʻi ʻē aʻe he pili like ka pregabalin a me gabapentin no ka subunit α2δ-1 recombinant kanaka (Ki = 32 nM a me 40 nM, kēlā me kēia).I kekahi hihia, ʻo ka pregabalin he 2 a 4 mau manawa ʻoi aku ka ikaika ma mua o ka gabapentin ma ke ʻano he analgesic a, i nā holoholona, ​​ʻike ʻia he 3 a 10 mau manawa ʻoi aku ka ikaika ma mua o ka gabapentin ma ke ʻano he anticonvulsant.