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 synthesis of gabapentin. a chemical synthesis of gabapentin has been described starting from 1,1-diacetyl hexane anhydride. history gabapentin was designed by researchers at parke-davis to be an analogue of the neurotransmitter gaba that could more easily cross the blood–brain barrier and was first described in 1975 by satzinger and hartenstein. under the brand name neurontin, it was first approved in may 1993, for the treatment of epilepsy in the united kingdom. approval by the u.s. food and drug administration followed in december 1993, for use as an adjuvant (effective when added to other antiseizure drugs) medication to control partial seizures in adults; that indication was extended to children in 2000. subsequently, gabapentin was approved in the united states for the treatment of postherpetic neuralgia in 2002. a generic version of gabapentin first became available in the united states in 2004. an extended-release formulation of gabapentin for once-daily administration, under the brand name gralise, was approved in the united states for the treatment postherpetic neuralgia in january 2011. society and culture united kingdom effective april 2019, the united kingdom reclassified the drug as a class c controlled substance. united states effective 1 july 2017, kentucky classified gabapentin as a schedule v controlled substance statewide. effective 9 january 2019, michigan also classified gabapentin as a schedule v controlled substance. gabapentin is scheduled v drug in other states such as west virginia, tennessee, alabama. off-label promotion although some small, non-controlled studies in the 1990s—mostly sponsored by gabapentin's manufacturer—suggested that treatment for bipolar disorder with gabapentin may be promising, the preponderance of evidence suggests that it is not effective. franklin v. parke-davis case main article: franklin v. parke-davis subsequent to the corporate acquisition of the original patent holder, the pharmaceutical company pfizer admitted that there had been violations of fda guidelines regarding the promotion of unproven off-label uses for gabapentin in the franklin v. parke-davis case (see below). while off-label prescriptions are common for a number of drugs, marketing of off-label uses of a drug is not. in 2004, warner-lambert (which subsequently was acquired by pfizer) agreed to plead guilty for activities of its parke-davis subsidiary, and to pay $430 million in fines to settle civil and criminal charges regarding the marketing of neurontin for off-label purposes. the 2004 settlement was one of the largest in u.s. history, and the first off-label promotion case brought successfully under the false claims act. reuters reported on 25 march 2010, that "pfizer inc violated federal racketeering law by improperly promoting the epilepsy drug neurontin ... under federal rico law the penalty is automatically tripled, so the finding will cost pfizer $141 million." the case stems from a claim from kaiser foundation health plan inc. that "it was misled into believing neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions. pfizer argued that kaiser physicians still recommend the drug for those uses", and that "the insurer's website also still lists neurontin as a drug for neuropathic pain." the wall street journal noted that pfizer spokesman christopher loder said, "we are disappointed with the verdict and will pursue post-trial motions and an appeal." he later added that "the verdict and the judge's rulings are not consistent with the facts and the law." gabasync gabasync, a treatment consisting of a combination of gabapentin and two other medications (flumazenil and hydroxyzine) as well as therapy, is an ineffective treatment promoted for methamphetamine addiction, though it had also been claimed to be effective for dependence on alcohol or cocaine. it was marketed as prometa. while the individual drugs had been approved by the fda, their off-label use for addiction treatment has not. gabasync was marketed by hythiam, inc. which is owned by terren peizer, a former junk bond salesman who has since been indicted for securities fraud relative to another company. hythiam charges up to $15,000 per patient to license its use (of which half goes to the prescribing physician, and half to hythiam). in november 2011, the results of a double-blind, placebo-controlled study (financed by hythiam and carried out at ucla) were published in the peer-reviewed journal addiction. it concluded that gabasync is ineffective: "the prometa protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving." barrons, in a november 2005 article entitled "curb your cravings for this stock", wrote "if the venture works out for patients and the investing public, it'll be a rare success for peizer, who's promoted a series of disappointing small-cap medical or technology stocks ... since his days at drexel". journalist scott pelley said to peizer in 2007: "depending and who you talk to, you're either a revolutionary or a snake oil salesman." 60 minutes, nbc news, and the dallas morning news criticized peizer after the company bypassed clinical studies and government approval when bringing to market prometa; the addiction drug proved to be completely ineffective. journalist adam feuerstein opined: "most of what peizer says is dubious-sounding hype". brand names gabapentin was originally marketed under the brand name neurontin. since it became generic, it has been marketed worldwide using over 300 different brand names. an extended-release formulation of gabapentin for once-daily administration was introduced in 2011, for postherpetic neuralgia under the brand name gralise. related drugs parke-davis developed a drug called pregabalin, which is related in structure to gabapentin, as a successor to gabapentin. another similar drug atagabalin has been unsuccessfully tried by pfizer as a treatment for insomnia. a prodrug form (gabapentin enacarbil) was approved by the u.s. food and drug administration (fda). recreational use gabapentin when taken in excess, can induce euphoria, a sense of calm, a marijuana- or benzodiazepine-like high, improved sociability (through disinhibition), and reduced alcohol or cocaine cravings. also known on the streets as "gabbies", gabapentin is increasingly abused and misused for these euphoric effects. about 1 percent of the responders to an internet poll and 22 percent of those attending addiction facilities had a history of abuse of gabapentin. gabapentin misuse, toxicity, and use in suicide attempts among adults in the us increased from 2013 to 2017. after kentucky's implementation of stricter legislation regarding opioid prescriptions in 2012, there was an increase in gabapentin-only and multi-drug use in 2012–2015. the majority of these cases were from overdose in suspected suicide attempts. these rates were also accompanied by increases in abuse and recreational use. withdrawal symptoms, often resembling those of benzodiazepine withdrawal, play a role in the physical dependence some users experience. its misuse predominantly coincides with the usage of other cns depressant drugs, namely opioids, benzodiazepines, and alcohol. veterinary use in cats, gabapentin can be used as an analgesic in multi-modal pain management, anxiety medication to reduce stress in cats for travel or vet visits, and anticonvulsant. veterinarians may prescribe gabapentin as an anticonvulsant and pain reliever in dogs. it is also used to treat chronic pain-associated nerve inflammation in horses and dogs. side effects include tiredness and loss of coordination but they generally go away within 24 hours.