HuagongsheHuagongshe Chemistry Print Report · For research reference only
Gabapentin
GABAPENTINE · NEURONTIN · GABAPENTIN HYDROCHLORIDE · 1-(Aminomethyl)-cyclohexaneacetic acid, Neurontin · GOE-3450 · Gabapentin API · 1-(AMINOMETHYL)CYCLOHEXANEACETIC ACID · 2-[1-(aminomethyl)cyclohexyl]acetic acid
Identifiers & Physical Properties
| CAS No. | 60142-96-3 |
|---|---|
| Molecular formula | C9H17NO2 |
| Average molar mass | 171.24 g/mol |
| Monoisotopic mass | 171.12592878 g/mol |
| SMILES | NCC1(CC(=O)O)CCCCC1 |
| InChIKey | UGJMXCAKCUNAIE-UHFFFAOYSA-N |
| PubChem CID | 3446 |
| ChEMBL | CHEMBL940 |
| ChEBI | CHEBI:42797 |
| EC No. | 262-076-3 |
| DTXSID | DTXSID0020074 |
Chemical & Physical Properties
| XLogP | -1.1 |
|---|---|
| Topological polar surface area | 63.3 |
| Hydrogen bond donors | 2 |
| Hydrogen bond acceptors | 3 |
| Rotatable bonds | 3 |
| Heavy atoms | 12 |
| Formal charge | 0 |
| Complexity | 162 |
| Chemical classes | Pharmaceutical |
| Drugs | Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antiepileptic |
| LogP (partition coefficient) | log Kow = -1.10 |
| Taste | Bitter |
| Color/Form | White to off-white crystalline solidcrystals from ethanol/ether |
| Solubility | >100mg/mLIn water, 4.49X10+3 mg/L at 25 °CFreely soluble in waterFreely soluble in alkaline and acidic solutions>25.7 [ug/mL] (The mean of the results at pH 7.4)H2O: 10 mg/mLwater: 100mM |
| Human Drugs | Breast FeedingLactationMilk, HumanAnticonvulsantsAntimanic AgentsGABA AgentsFDA approved drugs -> Active ingredientPharmaceuticals |
| Decomposition | Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx). |
| Melting point | 162-166 °Calso reported as 165-167 °C165 - 167 °C162°C |
| Physical Description | Solid |
| Stability/Shelf Life | Stable under recommended storage conditions. |
| Dissociation Constants | 3.7pKa1 = 3.68 at 25 °C (carboxylic acid)pKa2 = 10.70 (primary amine) |
| Boiling point | 314.4±15.0 °C(Predicted) |
| Density | 1.058±0.06 g/cm3(Predicted) |
| Flash point | 9℃ |
| Storage conditions | 2-8°C |
| Physical state | solid |
| pKa (acidity coefficient) | pKa1 (25°) 3.68pKa2 10.70 |
| Color | off-white |
| Merck | 14,4319 |
| BRN | 2359739 |
| BCS Class | 3 |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in distilled water may be stored at -20°C for up to 3 months. |
| Major applications | pharmaceutical (small molecule) |
| InChI | 1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12) |
| InChIKey | UGJMXCAKCUNAIE-UHFFFAOYSA-N |
| SMILES | NCC1(CCCCC1)CC(O)=O |
| CAS DataBase Reference | 60142-96-3(CAS DataBase Reference) |
| EWG's Food Scores | 1 |
| NCI Dictionary of Cancer Terms | gabapentin |
| FDA UNII | 6CW7F3G59X |
| NCI Drug Dictionary | gabapentin |
| ATC code | N03AX12 |
| EPA Substance Registry System | Cyclohexaneacetic acid, 1-(aminomethyl)- (60142-96-3) |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| Protein binding | <3% |
| Excreted unchanged in urine | ≈100% |
| Volume of distribution | 0.7(L/kg) |
| Biological half-life | 5-7 / 52 |
| GHS pictogram | GHS07,GHS08,GHS02,GHS06 |
| Signal word | Danger |
| GHS hazard statements | H225-H301+H311+H331-H370-H315-H319-H335-H360 |
| GHS precautionary statements | P210-P260-P280-P301+P310-P311-P302+P352+P312-P304+P340+P312-P370+P378-P403+P235-P201-P305+P351+P338-P308+P313-P261 |
| Target organs | Eyes,Central nervous system |
| Hazard symbols | T,Xi,F |
| Risk statements (R) | 61-36/37/38-39/23/24/25-23/24/25-11 |
| Safety statements (S) | 53-26-36/37/39-45-36-36/37-16 |
| UN transport number | UN3259 |
| Water hazard class (WGK) | 3 |
| RTECS number | GU6496000 |
| Hazard class | IRRITANTAcute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 3 OralFlam. Liq. 2STOT SE 1 |
| Customs code | 29224999 |
| Storage class | 3 - Flammable liquids |
| Hazardous substances data | 60142-96-3(Hazardous Substances Data) |
| Limited quantities | 5.0 kg (11 lbs) (solid) |
| Excepted quantities | Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L) |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 30.8% (32 of 104) of reports.DangerH315 (57.7%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 104 reports by companies from 23 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatory information | Gabapentin: Does not have an individual approval but may be used under an appropriate group standard |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including gabapentin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including gabapentin enacarbil, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Gabapentin enacarbil/ |
| Hazard Classes and Categories | Skin Irrit. 2 (57.7%) |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents. |
| Fire fighting procedures | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. |
| Storage conditions | Keep container tightly closed in a dry and well-ventilated place.Store Neurontin Tablets and Capsules at 25 °C (77 °F)excursions permitted between 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature]. Store Neurontin Oral Solution refrigerated, 2 °C to 8 °C (36 °F to 46 °F). |
| Cleanup methods | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Disposal methods | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubberContaminated packaging: Dispose of as unused product. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
| Personal Protective Equipment (PPE) | Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| Treatment | Gabapentin can be removed by hemodialysis. (L1712) |
| Interactions | When gabapentin is administered with morphine, patients should be observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depressionCoadministration of Neurontin with hydrocodone decreases hydrocodone exposure. The potential for alteration in hydrocodone exposure and effect should be considered when Neurontin is started or discontinued in a patient taking hydrocodone.The mean bioavailability of gabapentin was reduced by about 20% with concomitant use of an antacid (Maalox) containing magnesium and aluminum hydroxides. It is recommended that gabapentin be taken at least 2 hours following Maalox administration.Concomitant use of alcohol or other drugs that can cause sedation or dizziness can potentiate the CNS effects of gabapentin and generally should be avoided. In addition, alcohol can increase the rate of drug release from gabapentin enacarbil extended-release tablets and should be avoided in patients receiving this formulation. Concomitant use of opiate analgesics in patients receiving gabapentin may result in increased plasma concentrations of gabapentin and increase the risk of adverse CNS effects and respiratory depressiondosage adjustments may be required with such concomitant use. |
| Health effects | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
| Hepatotoxicity | Limited data are available on the hepatotoxicity of gabapentin. In clinical trials in diabetic neuropathy and epilepsy, therapy with gabapentin was not associated with an increased frequency of serum aminotransferase elevations or liver toxicity. Rare individual case reports of liver injury from gabapentin have been published, although the causal relationship of gabapentin with the liver injury was not always clear. The latency to onset in these reports was 1 to 8 weeks and associated with cholestatic pattern of enzyme elevations. Fever and rash have been described but not autoantibody formation. Reported cases have been mild to moderate in severity and self-limited in course. In view of the wide-scale use of gabapentin, liver injury with symptoms or jaundice is clearly quite rare. |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a structure estimation method(2), indicates that gabapentin is expected to have high mobility in soil(SRC). Experimental pKa values for gabapentin are 3.68 (carboxylic acid) and 10.70 (primary amine)(3), indicating that this compound will exist primarily as a zwitterion in the environment. Volatilization of gabapentin from moist soil surfaces is not expected to be an important fate process(SRC) since ionic compounds do not volatilize. Gabapentin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the Closed Bottle test, gabapentin was classified as not readily biodegradable(4), indicating that biodegradation is not an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a structure estimation method(2), indicates that gabapentin is not expected to adsorb to suspended solids and sediment(SRC). Experimental pKa values for gabapentin are 3.68 (carboxylic acid) 10.70 (primary amine)(3), indicating that this compound will exist primarily as a zwitterion in the environment. Therefore, vcolatilization from water surfaces is not expected(SRC) since ionic compounds do not volatilize. According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of -1.10(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using the Closed Bottle test, gabapentin was classified as not readily biodegradable(6), indicating that biodegradation is not an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), gabapentin, which has an estimated vapor pressure of 2.9X10-10 mm Hg at 25 °C((SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase gabapentin may be removed from the air by wet and dry deposition(SRC). Gabapentin was 80% eliminated after 128 minutes of direct UV irradiation(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Adverse effects | Gabapentin may cause certain adverse effects, which are listed below. |
| Exposure routes | Oral. Rapid. Absorbed in part by the L-amino acid transport system, which is a carrier-mediated, saturable transport systemas the dose increases, bioavailability decreases. Bioavailability ranges from approximately 60% for a 900 mg dose per day to approximately 27% for a 4800 milligram dose per day. Food has a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC). |
| Milk Concentrations | Gabapentin is distributed into human breast milk following oral administration. A nursed infant could be exposed to a maximum dose of approximately 1 mg/kg/day. |
| Toxicity summary | IDENTIFICATION AND USE: Gabapentin is an anticonvulsant structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA)the drug also possesses analgesic activity. Gabapentin enacarbil is a prodrug of gabapentin. Gabapentin is a white to off-white crystalline solid. Conventional (immediate-release) preparations of gabapentin are used in the management of seizure disorders and in the treatment of postherpetic neuralgia. Gabapentin enacarbil is commercially available as an extended-release tablet formulation for once-daily administration in the treatment of postherpetic neuralgia and primary restless legs syndrome. Gabapentin is also used in veterinary medicine in the treatment of seizures and as an analgesic for treating chronic pain in small animals. HUMAN EXPOSURE AND TOXICITY: Antiepileptic drugs (AEDs), including gabapentin increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Gabapentin can also cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with gabapentin. ANIMAL STUDIES: A lethal dose of gabapentin was not identified in mice and rats receiving single oral doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation, hypoactivity, or excitation. Gabapentin was administered orally to mice and rats in 2-year carcinogenicity studies. No evidence of drug-related carcinogenicity was observed in mice treated at doses up to 2000 mg/kg/day. In rats, increases in the incidence of pancreatic acinar cell adenoma and carcinoma were found in male rats receiving the highest dose (2000 mg/kg), but not at doses of 250 or 1000 mg/kg/day. When pregnant mice received oral doses of gabapentin (500, 1000, or 3000 mg/kg/day) during the period of organogenesis, increased incidences of skeletal variations were observed at the two highest doses. In studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day), during pregnancy, increased incidences of hydroureter and/or hydronephrosis were observed at all doses. Likewise, when pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60, 300, or 1500 mg/kg). Gabapentin did not demonstrate mutagenic or genotoxic potential in several in vitro and in vivo assays. It was negative in the Ames test and the in vitro HGPRT forward mutation assay in Chinese hamster lung cellsit did not produce significant increases in chromosomal aberrations in the in vitro Chinese hamster lung cell assayit was negative in the in vivo chromosomal aberration assay and in the in vivo micronucleus test in Chinese hamster bone marrowit was negative in the in vivo mouse micronucleus assayand it did not induce unscheduled DNA synthesis in hepatocytes from rats given gabapentin.At the federal level, gabapentin is not classified as a controlled substance, is regarded as a non-addictive medication, and is recognized by the Centers for Disease Control and Prevention (CDC) as a potential substitute for opioids in managing chronic pain. However, growing concerns about the potential for misuse are increasing. Several US states have moved gabapentin to the Schedule V controlled substance category. Gabapentin does not have a high risk of an overdose but can increase the euphoria caused by opioids and reduce drug withdrawals. An Australian study examined fatal gabapentinoid-related poisoning and discovered that concomitant other drug use is almost universal in such cases. Furthermore, gabapentin can bypass the blocking effects of addiction treatment medications and, unfortunately, does not appear in urine drug tests.Gabapentin interacts with cortical neurons at auxillary subunits of voltage-sensitive calcium channels. Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters. One of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of the hippocampus. This is mediated through its binding to presynaptic NMDA receptors. Other studies have shown that the antihyperalgesic and antiallodynic effects of gabapentin are mediated by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin has also been shown to bind and activate the adenosine A1 receptor. |
| Signs and Symptoms | Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation. |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of October 28, 2016: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | Based on an annual consumption of 4278.99 kg/yr, the estimated gabapentin elimination from primary and secondary treatment processes was 0.25 and 99%, respectively, from wastewater facilities in Spain in 2009, giving a predicted environmental occurrence of 41.62 ng/L(1). The compound was detected at a range of 15,034-18,474, 2592-21,417 and <0.6-1,879 ng/L in influent, final effluent and surface waters, respectively, in the UK(2). |
| Water hazard class (WGK) | 3 |
| RTECS number | GU6496000 |
| UN transport number | UN3259 |
| Customs code | 29224999 |
| Risk statements (R) | 61-36/37/38-39/23/24/25-23/24/25-11 |
| Signal word | Danger |
| GHS pictogram | GHS07,GHS08,GHS02,GHS06 |
| Hazard symbols | T,Xi,F |
| Safety statements (S) | 53-26-36/37/39-45-36-36/37-16 |
| Hazard class | IRRITANTAcute Tox. 3 DermalAcute Tox. 3 InhalationAcute Tox. 3 OralFlam. Liq. 2STOT SE 1 |
| Storage class | 3 - Flammable liquids |
| Target organs | Eyes,Central nervous system |
| GHS hazard statements | H225-H301+H311+H331-H370-H315-H319-H335-H360 |
| Limited quantities | 5.0 kg (11 lbs) (solid) |
| Excepted quantities | Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L) |
| GHS precautionary statements | P210-P260-P280-P301+P310-P311-P302+P352+P312-P304+P340+P312-P370+P378-P403+P235-P201-P305+P351+P338-P308+P313-P261 |
| Hazardous substances data | 60142-96-3(Hazardous Substances Data) |
Applications & Uses
Description
Gabapentin is a second- generation antiepileptic drug (AED) known under the proprietary brand name of Neurontin® (Pfizer, New York, NY) in the UK and USA.
Description
Gabapentin was introduced in 1993 in the UK and early 1994 in the USA as an adjunctive therapy in the treatment of refractory partial seizures and secondarily generalized tonic-clonic seizures. Although being a lipophilic analog of the neurotransmitter GABA, gabapentin appears to exert its anticonvulsive function by a GABA receptor independent mechanism, possibly involving the L-system amino acid transporter protein. Gabapentin easily crosses the blood brain barrier and exhibits a favorable pharmacokinetic profile with high tolerability. It does not interfere with the metabolism of other concomitant administered antiepileptic drugs, thus having a low potential for drug interactions. Studies are currently underway for the use of gabapentin as mono-therapy for the treatment of various seizures.
Description
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter that functions by binding to the GABA receptors located in the spinal cord. Gabapentin is a γ-aminobutyric acid (GABA) analogue that acts as an anticonvulsant with proven analgesic effects in various neuropathic pain syndromes such as Complex Regional Pain Syndrome type one (CRPS 1). It is also prescribed to multiple sclerosis patients to control dysesthesias and may be useful in reducing neuropathic pain caused by cancer and HIV infection. It does not bind to GABA receptors, does not influence neural uptake of GABA, and does not inhibit the GABA-metabolizing enzyme, GABA transaminase. Unlike GABA, which does not pass through the blood-brain barrier, gabapentin penetrates into the central nervous system and binds to the α2δ-type voltage-gated calcium channels. The mechanism for the analgesic and anticonvulsant effects of gabapentin are not known.
History
Gabapentin is a pharmacologically active amino acid, discovered by the pharmaceutical company Parke-Davis, now owned by Warner-Lambert, a division of Pfizer in 1974. Although it was first approved as a treatment for partial seizures in 1993, Pfizer pleaded guilty to illegally marketing gabapentin for unapproved uses in 2004 and was heavily fined by the US Department of Justice for defrauding public health care programs. When this adjunctive use was approved by the US Food and Drug Administration (FDA) in late 1993, Warner-Lambert released gabapentin under the brand name Neurontin, expecting it to make no more than $500,000. But the 2001 sales of Neurontin raked in $1.2 billion.
Uses
Gabapentin is an Amino acid structurally related to γ-Aminobutyric Acid (GABA), designed to cross the blood brain barrier. Used as an anticonvulsant.
Uses
selective H1-receptor antagonist
Uses
antipsychotic, 5HT2A antagonist
Uses
For the treatment of adult Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).
General Description
Gabapentin and its closely related analog pregabalin,(S)-3-isobutyl-GABA, are broad-spectrum anticonvulsantswith multiple mechanisms of action.24,51 Inaddition to modulating calcium influx and stimulateGABA biosynthesis as discussed earlier, they also competefor the biosynthesis of L-glutamic acid because oftheir structural similarity to L-leucine.51 Gabapentin andpregabalin have very little liability for causing metabolicbaseddrug–drug interactions, particularly when used incombination with other AEDs because they are not metabolizedin humans. More than 95% of the drug is excretedunchanged through the kidneys. However, there are somedifferences in their bioavailability. Unlike gabapentin,which exhibits 60% bioavailability when given in lowdoses because of intestinal uptake by a saturable smallneutral L-amino acid transporter, the absorption of pregabalinis almost complete (98%) and exhibits an ideal linear pharmacokinetic profile.24 This high bioavailability of pregabalincan be attributed to its closer structure similarity tothe essential amino acid, L-leucine.