Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabetic neuropathy, postherpetic neuralgia, and central pain. It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit.Sleepiness and dizziness are the most common side effects. Serious side effects include an increased risk of suicide, respiratory depression, and allergic reactions. Lower doses are recommended in those with kidney disease. Gabapentin acts by decreasing activity of a subset of calcium channels.Gabapentin was first approved for use in 1993. It has been available as a generic medication in the United States since 2004. In 2020, it was the tenth most commonly prescribed medication in the United States, with more than 49 million prescriptions. During the 1990s, Parke-Davis, a subsidiary of Pfizer, used a number of illegal techniques to encourage physicians in the United States to prescribe gabapentin for unapproved uses. They have paid out millions of dollars to settle lawsuits regarding these activities. Medical uses
Gabapentin is recommended for use in focal seizures and neuropathic pain. Gabapentin is widely prescribed off-label in the US and UK, for example, for the treatment of non-neuropathic pain, anxiety disorders and bipolar disorder. Seizures
Gabapentin is approved for the treatment of focal seizures; however, it is not effective for generalized epilepsy. Neuropathic pain
Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities.
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.