Gabapentin is a derivative of the neurotransmitter GABA (gamma-aminobutyric acid) but no effect on GABA receptors or converted or metabolized into GABA or a GABA antagonist nor an inhibitor of GABA reuptake.

Gabapentin shows no affinity for other receptors common as benzodiazepine, glutamate receptor, NMDA (N-methyl-D-aspartate) in quisqualato to kainate, a1, a2 or beta-adrenergic, adenosine A1 and A2, cholinergic, muscarinic, nicotinic, dopamine, histamine, serotonin, opiates, cannabinoids, voltage-gated calcium or sodium channels. Does not alter the uptake of dopamine, norepinephrine or serotonin.

Gabapentin binds apparently to specific receptors that are abundant in some areas of the neocortex and hippocampus. We have identified a protein to which it has a high affinity, a protein that is an auxiliary subunit calcium channel voltage-called alpha-2-delta.

The mechanism by which gabapentin exerts an analgesic action is unknown. In animal models of pain, this medication is particularly effective in the prevention of neuropathic pain (spinal nerve ligation, streptozotocin-induced diabetes, herpes zoster infection), but also prevents the pain associated with inflammatory processes. By contrast, gabapentin does not act on the immediate pain (for example in testing the rat’s tail, or abdominal contractions produced by the injection of acetic acid).

The bioavailability of gabapentin is not proportional to the dose: as the dose increases, bioavailability decreases. With doses of 900 mg / day divided in 3 administrations, the bioavailability reaches 60% decreasing to 27% with doses of 4,800 mg / day.

The administration of gabapentin with food increases the absorption slightly. The drug binds very little to plasma proteins (3%) with its apparent volume of distribution following a 150 mg intravenous dose of 58 ± 6 L. In patients with epilepsy, drug concentrations in cerebrospinal fluid are approximately 20% of plasma concentrations.

Gabapentin is not appreciably metabolized and eliminated by renal excretion. The elimination half-life is 5 to 7 hours and is not affected when given multiple doses. Both the plasma and the renal clearance proportional to creatinine clearance. The elimination of gabapentin is lower in patients with renal dysfunction in the elderly.

Gabapentin high is eliminated in the dialysis, so that in these patients and in patients with renal failure requires dose adjustments in Toxicity, carcinogenicity studies found a high incidence of pancreatic adenocarcinomas in male rats.

Gabapentin is unknown clinical relevance of this finding. In clinical studies in the treatment of epilepsy in patients 12 years, equivalent to 2085 years-patient drug exposure were reported 10 cases of new growths and worsening of pre-existing 11 tumors during or within 2 years after treatment with gabapentin.