Pregabalin si GABAA kapena GABAB receptor agonist.
Pregabalin ndi gabapentinoid ndipo amagwira ntchito poletsa njira zina za calcium.Makamaka ndi ligand wa malo othandizira a α2δ subunit ena amagetsi otengera ma calcium channels (VDCCs), ndipo potero amakhala ngati inhibitor wa α2δ subunit-containing VDCCs.Pali ma subunits a α2δ omwe amamangiriza mankhwala, α2δ-1 ndi α2δ-2, ndipo pregabalin amawonetsa kuyanjana kofanana kwa (ndi chifukwa chake kusowa kwa kusankha pakati) masamba awiriwa.Pregabalin imasankha pomanga gawo la α2δ VDCC.Ngakhale kuti pregabalin ndi GABA analogue, sichimangirira ku GABA receptors, sichisintha kukhala GABA kapena GABA receptor agonist mu vivo, ndipo sichimayendetsa mwachindunji kayendedwe ka GABA kapena kagayidwe kake.Komabe, pregabalin yapezeka kuti ikupanga kuwonjezeka kodalira kwa mlingo wa L-glutamic acid decarboxylase (GAD), enzyme yomwe imayambitsa kupanga GABA, motero ikhoza kukhala ndi zotsatira zina za GABAergic mwa kuonjezera milingo ya GABA mu ubongo.Pakalipano palibe umboni wosonyeza kuti zotsatira za pregabalin zimayendetsedwa ndi njira ina iliyonse kupatula kuletsa kwa α2δ-containing VDCCs.Mogwirizana, kuletsa kwa α2δ-1-containing VDCCs ndi pregabalin kumawoneka kuti kumayambitsa anticonvulsant, analgesic, ndi anxiolytic zotsatira.
Ma endogenous α-amino acids L-leucine ndi L-isoleucine, omwe amafanana kwambiri ndi pregabalin ndi ma gabapentinoids ena pamapangidwe amankhwala, amawoneka ngati ma ligand a subunit ya α2δ VDCC yokhala ndi mgwirizano wofanana ndi ma gabapentinoids (mwachitsanzo, IC50 = 71 nM ya L- isoleucine), ndipo alipo mu cerebrospinal madzimadzi pa micromolar ndende (mwachitsanzo, 12.9 μM kwa L-leucine, 4.8 μM kwa L-isoleucine).Zakhala zikunenedwa kuti akhoza kukhala ma ligands amtundu wa subunit komanso kuti akhoza kupikisana ndi zotsatira za gabapentinoids.Mogwirizana, ngakhale ma gabapentinoids monga pregabalin ndi gabapentin ali ndi ma nanomolar affinities a α2δ subunit, mphamvu zawo mu vivo zili m'munsi mwa micromolar range, ndipo mpikisano womanga ndi L-amino acids wanenedwa kuti ndiwo amachititsa kusiyana kumeneku.

Pregabalin adapezeka kuti ali ndi 6-fold high kuyanjana kuposa gabapentin kwa α2δ yokhala ndi ma VDCCs mu kafukufuku wina.Komabe, kafukufuku wina adapeza kuti pregabalin ndi gabapentin anali ndi zofananira zofananira za α2δ-1 subunit yamunthu (Ki = 32 nM ndi 40 nM, motsatana).Mulimonsemo, pregabalin imakhala yamphamvu 2 mpaka 4 kuposa gabapentin ngati mankhwala oletsa ululu ndipo, mwa nyama, ikuwoneka kuti ili ndi mphamvu 3 mpaka 10 kuposa gabapentin ngati anticonvulsant.