Although the efficacy of gabapentin for insomnia has not been established, it does alleviate sleep disorder in patients with medical illness.Gabapentin does not appear to provide benefit for bipolar disorder, complex regional pain syndrome, post-surgical pain, or tinnitus, or prevent episodic migraine in adults. Contraindications
Gabapentin should be used carefully and at lower doses in people with kidney problems due to possible accumulation and toxicity. It is unclear if it is safe during pregnancy or breastfeeding. Side effects
Dizziness and somnolence are the most frequent side effects. Fatigue, ataxia, peripheral edema (swelling of extremities), and nystagmus are also common. Gabapentin is associated with a weight gain of 2.2 kg after 1.5 months of use. Case studies indicate that it may cause anorgasmia and erectile dysfunction, as well as myoclonus that disappear after discontinuing gabapentin or replacing it with other medication. DRESS, anaphylaxis, respiratory depression, and increased suicide behavior are the rare but serious side effects. Suicide
The gabapentin label contains a warning of an increased risk of suicidal thoughts and behaviors. According to an insurance claims database study, gabapentin use is associated with about 40% increased risk of suicide, suicide attempt and violent death as compared with a reference anticonvulsant drug topiramate. The risk is increased for both bipolar disorder and epilepsy patients. Another study has shown an approximately doubled rate of suicide attempts and self-harm in patients with bipolar disorder who are taking gabapentin versus those taking lithium.
Due to its low lipophilicity, gabapentin requires active transport across the blood–brain barrier. The LAT1 is highly expressed at the blood–brain barrier and transports gabapentin across into the brain. As with intestinal absorption mediated by an amino acid transporter, the transport of gabapentin across the blood–brain barrier by LAT1 is saturable. Gabapentin does not bind to other drug transporters such as P-glycoprotein (ABCB1) or OCTN2 (SLC22A5). It is not significantly bound to plasma proteins (<1%).Gabapentin undergoes little or no metabolism.Gabapentin is eliminated renally in the urine. It has a relatively short elimination half-life, with the reported average value of 5 to 7 hours. This value changes with increasing doses, from 5.4 hours for a 200 mg single dose, to 8.3 hours for a 1,400 mg dose. Because of its short elimination half-life, gabapentin must be administered 3 to 4 times per day to maintain therapeutic levels. Gabapentin XR (brand name Gralise) is taken once a day. Chemistry
Gabapentin is a 3,3-disubstituted derivative of GABA. Therefore, it is a GABA analogue, as well as a γ-amino acid. Specifically, it is a derivative of GABA with a pentyl disubstitution at 3 position, hence, the name - gabapentin, in such a way as to form a six-membered ring. After formation of the ring, the amine and carboxylic groups are not in the same relative positions as they are in the GABA; they are more conformationally constrained. Synthesis
A chemical synthesis of gabapentin has been described starting from 1,1-diacetyl hexane anhydride.