We previously found that the endogenous anticonvulsant adenosine, acting through A _2A and A ₃ adenosine receptors (ARs), alters the stability of currents (I _GABA ) generated by GABA _A receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I _GABA expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA _A receptors revealed instability, manifested by a large I _GABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A _2A antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A ₃ receptor antagonist (ANR235) significantly improved I _GABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I _GABA rundown on ANR94 treatment. Our findings indicate that antagonizing A _2A and A ₃ receptors increases the I _GABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.