The mechanism of action for both Neurontin (gabapentin) and Lyrica (pregablin) is poorly understood. There is an important neuro transmitter in the brain called GABA and both these medications have structural similarities to GABA. However, they work on slightly different receptors in the brain. For a more technical discussion of the mechanism of both these medications I will paraphrase the reference Micromedex 2.0
“Pregabalin is a GABA analog that strongly binds to the alpha(2)-delta site (a subunit of voltage-gated calcium channels) in central nervous system tissues. Binding to the alpha(2)-delta subunit may be involved in pregabalin’s effects on neuropathic pain and seizure control. Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function, however the exact mechanism of action is unknown”
“Gabapentin is structurally related to the neurotransmitter GABA; however, gabapentin and its metabolites do not bind to GABA (A) or GABA (B) receptors or influence the degradation or uptake of GABA it has been suggested the mechanism of action may be by gabapentin preventing thrombospondin from binding to alpha 2 delta-1 “
In summary, we don’t quite know how they work. However, they do seem to have similar effects on nerve related pain. However, tolerability and effectiveness can vary ignorantly among individuals and if someone finds one ineffective the other is still worth trying.