Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not modify GABAA or GABAB radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation.
Gabapentin has no activity at GABAA or GABAB receptors of GABA uptake carriers of the brain, but instead interacts with a high-affinity binding site in brain membranes (an auxiliary subunit of voltage-sensitive Ca2+ channels.) The exact mechanism of action is unknown.
In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain including neocortex and hippocampus.
In vitro, gabapentin has many pharmacological actions including modulating the action of the GABA synthetic enzyme, increasing non-synaptic GABA responses from neural tissue, and reduction of the release of several mono-amine neurotransmitters.
Adjunctive therapy in partial epilepsy with or without secondary generalisation not satisfactorily controlled with other antiepileptics
Neuropathic pain e.g. trigeminal neuralgia, post-herpetic neuralgia
Side effects: diarrhoea, dry mouth, dyspepsia, nausea, vomiting; peripheral oedema; dizziness, drowsiness, anxiety, abnormal gait, amnesia, ataxia, nystagmus, tremor, asthenia, paraesthesia, emotional lability, hyperkinesia; weight gain; dysarthria, arthralgia; diplopia, amblyopia; rash, purpura.
Less commonly: constipation, flatulence, dyspnoea, confusion, impotence, and leucopenia
Rarely: pancreatitis, depression, psychosis, headache, myalgia, and urinary incontinence; hepatitis, jaundice, chest pain, palpitation, movement disorders, thrombocytopenia, tinnitus, acute renal failure, and alopecia also reported.
avoid sudden withdrawal (may cause anxiety, insomnia, nausea, pain and sweating—taper off over at least 1 week); history of psychotic illness, elderly (may need to reduce dose), renal impairment, diabetes mellitus, false positive readings with some urinary protein tests.
Pregnancy and breast-feeding
During pregnancy, total plasma concentrations of antiepileptics (particularly of phenytoin) may fall, particularly in the later stages but free plasma concentrations may remain the same (or even rise). There is an increased risk of teratogenicity associated with the use of antiepileptic drugs (reduced if treatment is limited to a single drug). In view of the increased risk of neural tube and other defects associated, in particular, with carbamazepine, oxcarbazepine, phenytoin and valproate women taking antiepileptic drugs who may become pregnant should be informed of the possible consequences. Those who wish to become pregnant should be referred to an appropriate specialist for advice. Women who become pregnant should be counselled and offered antenatal screening (alpha-fetoprotein measurement and a second trimester ultrasound scan).
To counteract the risk of neural tube defects adequate folate supplements are advised for women before and during pregnancy; to prevent recurrence of neural tube defects, women should receive folic acid 5 mg daily this dose may also be appropriate for women receiving antiepileptic drugs.