Table 2.

The α2δ1-mediated effects of gabapentinoids

Molecular target	Mechanism	Effect	References
VGCCs	inhibition of calcium influx into the neuron and decreases its excitability	anti-seizures	[115]
presynaptic proteins engaged in the organization of glutamatergic synapses	interference with the formation and maturation of glutamatergic synapses	anti-epileptogenic?	[118]
neurexin-1α, and adhesion molecules (thrombospondins)	inhibition of aberrant excitatory synaptogenesis	analgesia, detrimental effect in the absence epilepsy	[8, 120, 122]
AMPAR	controlling the subunit composition and Ca2+ permeability of postsynaptic AMPARs	analgesia	[121]
NMDAR	interference with the phosphorylation of NMDAR, in this way, affecting neuroplasticity	anti-epileptogenic?	[122]
PI3K/Akt/mTOR pathway	preventing the oxidative stress-related autophagy via the activation of the PI3K/Akt/mTOR pathway	neuroprotective, anti-epileptogenic?	[123]

VGCCs - voltage-gated Ca2 + channels, AMPAR - α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, NMDAR– N-methyl-D-aspartate receptor, PI3K/Akt/mTOR - the phosphoinositide 3 kinase (PI3K)/Akt/mammalian (or mechanistic) target of the rapamycin (mTOR) pathway