Introduction The combined use of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) enables a direct investigation of cortical-evoked responses in humans. The physiology of the peaks characterizing the TMS-evoked EEG responses has not been clearly elucidated yet. EEG is able to detect fast-inhibitory post synaptic potentials (fIPSPs, Objectives In the present study we characterized the pharmaco-physiology of TEPs in healthy volunteers by using two GABA-A receptors positive modulators: alprazolam and zolpidem. The main aim of the study was to test to which extent early TEPs are affected by fast inhibitory neurotransmission through the GABA-A receptor. Materials and methods Twenty healthy subjects participated in a pseudorandomized, placebo-controlled, double-blind crossover design, using a single oral dose of alprazolam (1 mg), a classical benzodiazepine preferentially binding on alpha1, alpha2, alpha3 and alpha5 subunit bearing subtypes of the GABA-A receptor, and zolpidem (10 mg), which mainly binds at the alpha1 subtype. TEPs were recorded by TMS-EEG before and 90 min after drug administration and the effects of the drugs on the TEP amplitudes were statistically evaluated. Results A non parametric cluster-based permutation analysis of amplitudes at channel-level was run for placebo, alprazolam and zolpidem administration. Both alprazolam and zolpidem, increased the amplitude of the negative potential at 45 ms after stimulation (N45). Moreover, a strong positive correlation was found between their modulation on the N45 magnitude. In addition, alprazolam but not zolpidem decreased the amplitudes of the later TEPs, in particular, the negative at 100 ms (N100) and the positive at 180 ms (P180). Conclusion We provide first-time evidence that the N45 potential may reflect a biological marker of alpha1 containing GABA-A receptor activity. The broader modulation of several TEP components by alprazolam could be explained by its wider pharmacological profile, as it is responsible for the activation of several subtypes of GABA-A receptors.