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INN: Pregabalin
Pregabalin ball-and-stick model.png
Systematic (IUPAC) name
(S)-3-(aminomethyl)-5-methylhexanoic acid
Clinical data
Pronunciation /priˈɡæbəln/
Trade names originally Lyrica, many names worldwide[2]
AHFS/ Monograph
MedlinePlus a605045
License data
  • AU: B3
  • US: C (Risk not ruled out)
Physical: Moderate[1]
Psychological: Moderate[1]
Routes of
By mouth
Legal status
Legal status
Pharmacokinetic data
Bioavailability High (≥90% rapidly absorbed; administration with food has no significant effect on bioavailability)[3]
Protein binding Nil
Metabolites N-methylpregabalin[3]
Onset of action 1.5 hours (3 hours with food)[4]
Biological half-life 6.3 hours[4]
Excretion Renal (90% as unchanged drug; minor metabolites)[4]
CAS Number 148553-50-8 YesY
ATC code N03AX16 (WHO)
PubChem CID 5486971
DrugBank DB00230 YesY
ChemSpider 4589156 YesY
UNII 55JG375S6M YesY
KEGG D02716 YesY
Synonyms β-isobutyl-γ-Aminobutyric acid, 3-isobutyl GABA
Chemical data
Formula C8H17NO2
Molar mass 159.23 g.mol−1
 NYesY (what is this?)  (verify)

Pregabalin (PGN) marketed under the brand name Lyrica among others, is a medication used to treat epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder.[5][6][7] Its use for epilepsy is as an add-on therapy for partial seizures with or without secondary generalization in adults.[8] Some off-label uses of pregabalin include, restless leg syndrome, migraine, social phobia, panic disorder, mania, bipolar disorder, and alcohol withdrawal.[9][10]

Common side effects include: sleepiness, confusion, trouble with memory, poor coordination, dry mouth, problem with vision, and weight gain.[6] Potentially serious side effects include angioedema, drug misuse, and an increased suicide risk.[6] It is moderately addictive both physically and psychologically.[1]

Pregabalin is a 3-substituted derivative of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).[11][12] Pregabalin is a potent gabapentinoid and a close structural analogue of GABA (see GABA analogue), as well as of 4-Methylpregabalin, gabapentin, gabapentin enacarbil, GABOB, baclofen, and phenibut.[13][14] Pregabalin binds to the α2δ subunit of voltage-gated calcium channels (VGCCs) and modulates calcium influx at the nerve terminals, which may account for its therapeutic effect on neuropathic pain, anxiety, and seizures.[4][15]

Pregabalin has potential to be misused and abuse of the drug may lead to physical and psychological dependence. The Drug Enforcement Administration placed pregabalin, including its salts, and all products containing pregabalin into Schedule V of the Controlled Substances Act.[16][17][18] There is to be no generic version available in the United States until 2018.[19] A generic version is available in Canada and the United Kingdom.[20][21] In the US it costs about 300-400 USD per month.[6]

Medical uses[edit]

A package of 150 mg pregabalin capsules (Finland)


Pregabalin is useful when added to other treatments, when those other treatments are not controlling partial epilepsy.[22] Its use alone is less effective than some other seizure medications.[23]

It is unclear how it compares to gabapentin for this use.[23]

Neuropathic pain[edit]

The European Federation of Neurological Societies recommends pregabalin as a first line agent for the treatment of pain associated with diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain.[24] A minority obtain substantial benefit, and a larger number obtain moderate benefit.[25] Other first line agents, including gabapentin and tricyclic antidepressants, are given equal weight as first line agents, and unlike pregabalin, are available as less expensive generics.[26]

Pregabalin is not recommended for certain other types of neuropathic pain such as pain that of trigeminal neuralgia or HIV infection[27] and its use in cancer-associated neuropathic pain is controversial.[27] There is no evidence for its use in the prevention of migraines and gabapentin has been found not to be useful.[28] It has been examined for the prevention of post-surgical chronic pain, but its utility for this purpose is controversial.[29][30]

Pregabalin is generally not regarded as efficacious in the treatment of acute pain.[25] In clinical trials examining the utility of pregabalin for the treatment of acute post-surgical pain, no effect on overall pain levels was observed, but people did require less morphine and had fewer opioid-related side effects.[29] Several possible mechanisms for pain improvement have been discussed.[31]

Anxiety disorders[edit]

The World Federation of Biological Psychiatry recommends pregabalin as one of several first line agents for the treatment of generalized anxiety disorder, but recommends other agents such as SSRIs as first line treatment for obsessive-compulsive disorder and post-traumatic stress disorder.[32] It appears to have anxiolytic effects similar to benzodiazepines with less risk of dependence.[33][34]

Therapeutic effects of pregabalin appear after 1 week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychosomatic anxiety symptoms[35] Long-term trials have shown continued effectiveness without the development of tolerance, and, in addition, unlike benzodiazepines, it has a beneficial effect on sleep and sleep architecture, characterized by the enhancement of slow-wave sleep.[35] and produces less severe cognitive and psychomotor impairment compared to those drugs; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.[35][36]

Side effects[edit]

Pregabalin has been shown to produce therapeutic effects that are similar to other controlled substances. In a study with recreational users of sedative and hypnotic drugs, a 450 mg dose of pregabalin resulted in subjective ratings of a "good drug effect" and "high" and "liking" similar to 30 mg of diazepam. In clinical studies, pregabalin showed a side effect profile similar to other central nervous system depressants.[37]

Adverse drug reactions associated with the use of pregabalin include:[38][39]


Following abrupt or rapid discontinuation of pregabalin, some people reported symptoms suggestive of physical dependence. The FDA determined that the substance dependence profile of pregabalin, as measured by a patient physical withdrawal checklist, was quantitatively less than benzodiazepines.[37] Even people who have discontinued short term and or long term use of pregabalin have experienced withdrawal symptoms, including insomnia, headache, nausea, anxiety, diarrhea, flu like symptoms, nervousness, major depression, pain, convulsions, hyperhidrosis and dizziness.[41]


Several renal failure patients developed myoclonus while receiving pregabalin, apparently as a result of gradual accumulation of the drug. Acute overdosage may be manifested by somnolence, tachycardia and hypertonicity. Plasma, serum or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients.[42][43][44]

Drug interactions[edit]

No interactions have been demonstrated in vivo. The manufacturer notes some potential pharmacological interactions with opioids, benzodiazepines, barbiturates, ethanol (alcohol), and other drugs that depress the central nervous system. ACE inhibitors may enhance the adverse/toxic effect of Pregabalin. Antidiabetic Agents (Thiazolidinedione): Pregabalin may enhance the fluid-retaining effect of Antidiabetic Agents (Thiazolidinedione).[45]


Structure of pregabalin, gabapentin, and GABA


Pregabalin is a potent ligand for the α2δ subunit of voltage-gated calcium channels in the central nervous system.[46][47] Pregabalin possesses analgesic, anticonvulsant, and anxiolytic activity.[48] Although, pregabalin is an analogue of GABA, it does not bind directly to GABAA, GABAB, or benzodiazepine receptors. Nor does it block sodium channels and is not active at opioid receptors. Gabapentinoids, such as pregabalin, are α2δ subunit voltage-gated calcium channel modifiers that affect GABA. In contrast to the distribution of α2δ-1 and α2δ-2 subunits binding correlates partially with GABAergic neurons.[49] Reports concerning the effects of pregabalin on neural GABA concentrations are conflicting.[50][51][52] Pregabalin increases the density of GABA transporter proteins and increases the rate of functional GABA transport.[53]

Both α2δ subunit binding sites are also known for three other different gabapentinoids. That being gabapentin, gabapentin enacarbil, and phenibut. Recently, phenibut, a close analogue of pregabalin, has been found to similarly bind to the α2δ subunit of voltage-gated calcium channels and phenibut inhibits these channels similarly to gabapentin and pregabalin.[54] Baclofen has also been found to do this, but relatively weakly.[54] Moreover, it has been found that the antinociceptive effects of phenibut in rodents are mediated not by GABAB receptor but by blockade of α2δ subunit-containing voltage-gated calcium channels, implicating this action as an important mediator of the effects of phenibut.[54] Phenibut has the same structure of baclofen (lacking only a chlorine atom in the para-position of the phenyl group) and includes the phenylethylamine structure. Pregabalin has instead the phenyl group substituted with the isobutyl group. Making both phenibut and baclofen close analogues of pregabalin.[55] As such, phenibut is a gabapentinoid.[46][47][56]

Pregabalin is a 3–10 times more potent anticonvulsant and 2–4 times more potent analgesic than gabapentin.[57][58]

Pregabalin is 6 times more potent than gabapentin in binding affinity.[59][60][61]

The biological half-life for pregabalin is 6.3 hours.[4]



Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within one hour. Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 to 30% and a delay in Tmax (time to reach Cmax) to approximately 3 hours.[4] Administration with food, however, has no clinically significant effect on the extent of absorption.[3]


Pregabalin has been shown to cross the blood–brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the volume of distribution of pregabalin for an orally administered dose is approximately 0.56 L/kg and is not bound to plasma proteins.[3]


Pregabalin undergoes negligible metabolism in humans.[62] In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methylpregabalin.[3]


Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.[3] Renal clearance of pregabalin is 73 mL/minute.[63]


Pregabalin was synthesized in 1990 as an antiepileptic. It was invented by medicinal chemist Richard Bruce Silverman at Northwestern University in the United States.[64] The drug was approved in the European Union in 2004. Pregabalin received U.S. FDA approval for use in treating epilepsy, diabetic neuropathic pain, and postherpetic neuralgia in December 2004, and appeared on the U.S. market in fall 2005.[65]

In June 2007, the FDA approved Lyrica as a treatment for fibromyalgia. It was the first drug to be approved for this indication and remained the only one until duloxetine gained FDA approval for the treatment of fibromyalgia in June 2008.[66]

Generic versions of pregabalin became available in Russia in 2011,[67] in Canada in 2013, Iceland 2014,[68] and are expected to become available in the European Union and the U.S. in 2016 and 2018 respectively.[69]

Society and culture[edit]

Legal status[edit]

Regulatory approval[edit]

In the United States, the Food and Drug Administration (FDA) has approved pregabalin for adjunctive therapy for adults with partial onset seizures, management of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy, and the treatment of fibromyalgia.[73] Pregabalin has also been approved in the European Union and Russia (but not in US) for treatment of generalized anxiety disorder.[74][75]


Pregabalin is marketed by Pfizer under the trade name Lyrica. Pfizer described in an SEC filing that the drug could be used to treat epilepsy, postherpetic neuralgia, diabetic peripheral neuropathy and fibromyalgia. Lyrica was promoted for other uses which had not been approved by medical regulators up until 2009. For this practice, with three other drugs, Pfizer was fined a record amount of US$2.3 billion by the Department of Justice.[76] Lyrica sales reached a record US$3.063 billion in 2010.[77] Lyrica is one of four drugs which Pharmacia & Upjohn, a subsidiary of Pfizer, in 2009 pleaded guilty to misbranding "with the intent to defraud or mislead". Pfizer agreed to pay US$2.3 billion (GB£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer illegally promoted the drugs and caused false claims to be submitted to government healthcare programs for uses that were not approved by the U.S. Food and Drug Administration (FDA).[76]

Intellectual property[edit]

Northwestern University invented pregabalin and holds a patent on it, which it exclusively licensed to Pfizer.[78][79] That patent, along with others, was challenged by generic manufacturers and was upheld in 2014, giving Pfizer exclusivity for Lyrica in the US until 2018.[80][81]


In the United States as of 2015 the cost is between 3.69 and 5.52 USD per 150 mg tablet.[82]

See also[edit]


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External links[edit]