Pregabalin ba GABAA ko GABAB agonist ba ne.
Pregabalin gabapentinoid ne kuma yana aiki ta hanyar hana wasu tashoshi na calcium. Musamman ligand ne na rukunin rukunin rukunin yanar gizo na α2δ na wasu tashoshin calcium masu dogaro da wutar lantarki (VDCCs), kuma ta haka ne ke aiki a matsayin mai hana α2δ subunit-dauke da VDCCs. Akwai nau'ikan α2δ masu ɗaure ƙwayoyi guda biyu, α2δ-1 da α2δ-2, kuma pregabalin yana nuna alaƙa iri ɗaya don (saboda haka rashin zaɓi tsakanin) waɗannan rukunin yanar gizon guda biyu. Pregabalin zaɓi ne a cikin ɗaurin sa ga sashin α2δ VDCC. Duk da cewa pregabalin analog ne na GABA, baya ɗaure ga masu karɓar GABA, baya canzawa zuwa GABA ko wani agonist mai karɓar GABA a cikin vivo, kuma baya daidaita jigilar GABA ko metabolism kai tsaye. Koyaya, an gano pregabalin don samar da haɓaka mai dogaro da kashi a cikin maganganun kwakwalwa na L-glutamic acid decarboxylase (GAD), enzyme da ke da alhakin haɗa GABA, don haka yana iya samun wasu tasirin GABAergic kai tsaye ta hanyar haɓaka matakan GABA a cikin kwakwalwa. A halin yanzu babu wata shaida cewa tasirin pregabalin yana yin sulhu ta kowace hanya banda hanawa na α2δ-dauke da VDCCs. Dangane da, hanawa na α2δ-1-dauke da VDCCs ta hanyar pregabalin ya bayyana yana da alhakin anticonvulsant, analgesic, da tasirin anxiolytic.
L-leucine na α-amino acid L-leucine da L-isoleucine, waɗanda suke kama da pregabalin da sauran gabapentinoids a cikin sigar sinadarai, alamun ligands na α2δ VDCC subunit tare da alaƙa iri ɗaya kamar gabapentinoids (misali, IC50 = 71 nM don L- isoleucine), kuma suna kasancewa a cikin ruwan cerebrospinal na ɗan adam a ƙananan ƙwayoyin micromolar (misali, 12.9 μM na L-leucine, 4.8 μM na L-isoleucine). An yi la'akari da cewa ƙila su kasance masu haɗin gwiwa na ƙarshen subunit kuma suna iya yin adawa da tasirin gabapentinoids. Dangane da, yayin da gabapentinoids kamar pregabalin da gabapentin suna da alaƙar nanomolar ga sashin α2δ, ƙarfin su a cikin vivo suna cikin ƙaramin ƙaramin micromolar, kuma an ce gasa don ɗaure ta L-amino acid na ƙarshe zai iya haifar da wannan rashin daidaituwa.

An gano Pregabalin yana da kusancin ninki 6 mafi girma fiye da gabapentin don α2δ mai ƙunshe da VDCCs a cikin bincike ɗaya. Koyaya, wani binciken ya gano cewa pregabalin da gabapentin suna da alaƙa iri ɗaya ga ɗan adam recombinant α2δ-1 subunit (Ki = 32 nM da 40 nM, bi da bi). A kowane hali, pregabalin yana da ƙarfi fiye da sau 2 zuwa 4 fiye da gabapentin a matsayin maganin analgesic kuma, a cikin dabbobi, ya bayyana yana da ƙarfi fiye da 3 zuwa 10 fiye da gabapentin a matsayin anticonvulsant.