Which of the following mechanisms is MOST likely responsible for the analgesic effects of gabapentin?
(A) Acting as an agonist at the γ-aminobutyric acid (GABA) receptor
(B) Blocking N-methyl-D-aspartate (NMDA) receptors
(C) Blocking voltage-gated calcium channels
Though gabapentin and pregabalin are structural analogs of GABA, they are not active at the GABA receptor. Gabapentin is extensively used for the treatment of neuropathic pain conditions. Its mechanism of action is thought to be mediated by blocking voltage-gated calcium channels and reducing calcium influx. By blocking calcium influx, gabapentin reduces the release of excitatory neurotransmitters like glutamate, substance P, norepinephrine, and calcitonin gene-related peptide from primary nociceptive afferents, thereby modulating nociceptive transmission. Gabapentin has been used to treat neuropathic pain conditions associated with diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, complex regional pain syndrome, and painful peripheral neuropathies associated with cancer.
Gabapentin was initially approved by the U.S. Food and Drug Administration as an anticonvulsant, but it is now widely used off-label in conjunction with other medications for the management of pain. The use of gabapentin in enhanced recovery protocols has become more controversial given recent data suggesting that the opioid-sparing effect is minimal, while the risk for postoperative respiratory depression may be increased.
Gabapentin does not block the NMDA receptor.
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Answer: C
