Gabapentin
2-[1-(aminomethyl)cyclohexyl]acetic acid
Overview
Gabapentin belongs to Depressants.
Effects
- At therapeutic doses: reduced neuropathic pain and seizure frequency, commonly with drowsiness, dizziness and mild unsteadiness.
- At higher or recreational doses: alcohol-like disinhibition, relaxation, sociability and mild euphoria, sometimes with a 'floaty' or mildly dissociative quality. Effects are more pronounced in people with low tolerance.
- Onset is slow (roughly 30 minutes to 2 hours) and effects are long (about 6–10 hours), because absorption is saturable, very large single doses give diminishing returns while still adding side effects.
Dosing & duration
Oral (capsules, tablets or solution). Non-medical use is also oral.. Gabapentin's oral absorption is saturable, so bioavailability falls as the dose rises and very large single doses give diminishing effect while still adding side effects. The figures below are commonly cited reference ranges, not a recommendation or a 'safe' dose. The critical harm-reduction point is combination: gabapentin taken with opioids, benzodiazepines or alcohol markedly increases the risk of respiratory depression and death, even at amounts each would tolerate alone. Dependence develops with regular use and abrupt cessation can trigger seizures: taper, do not stop suddenly.
Dose ranges
200 mg
200–900 mg
900–1500 mg
1500–2400 mg
2400 mg +
Duration
30–120 minutes
6–10 hours
Grogginess, with regular use, tolerance, dependence and a withdrawal syndrome (seizure risk on abrupt cessation)
Chemical & Physical Properties
| Formula | C9H17NO2 |
| Molar mass | 171.24 g/mol |
| State | Solid |
| Melting point | 162–166 °C, also reported as 165–167 °C |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | 3.7 |
| LogP | 1.25 |
| Solubility | >100mg/mL, In water, 4.49×10³ mg/L at 25 °C, Freely soluble in water |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 60142-96-3 |
| CAS (enantiomer) | |
| PubChem CID | 3446 |
| InChIKey | UGJMXCAKCUNAIE-UHFFFAOYSA-N |
| InChI | InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12) |
| SMILES | C1CCC(CC1)(CC(=O)O)CN |
Synonyms
- Neurontin
- Gralise
- Gabapentin
Pharmacodynamics & Biochemistry
Gabapentin is a structural analogue of the neurotransmitter GABA, but, despite its name and design, it does not bind GABA receptors, is not converted to GABA, and has no meaningful effect on GABA uptake or metabolism. It is used mainly as an anticonvulsant and for neuropathic pain. Its established primary mechanism is high-affinity binding to the α2δ auxiliary subunit of voltage-gated calcium channels (α2δ-1 and α2δ-2). This reduces calcium influx at nerve terminals and dampens the release of excitatory neurotransmitters such as glutamate, noradrenaline and substance P, which underlies its analgesic and anticonvulsant effects. Gabapentin was more recently shown to be a potent activator of the KCNQ3 (Kv7.3) and KCNQ5 (Kv7.5) voltage-gated potassium channels. Opening these channels enhances the outward neuronal 'M-current' and lowers excitability: a second mechanism that may contribute to its clinical effects, and the basis of the binding data shown below. Gabapentin has a favourable but quirky pharmacokinetic profile: it is absorbed by a saturable amino-acid transporter, so oral bioavailability falls as the dose rises (dose-dependent, non-linear kinetics). It is essentially not metabolised and is eliminated unchanged by the kidneys, so doses must be reduced in renal impairment.
Biological targets
- VGCC α2δ
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| Kv7.5 | pEC50 8.7 | Human |
| Kv7.3 | pEC50 8.3 | Human |
Pharmacokinetics
| Bioavailability | Oral, saturable and dose-dependent (≈60% falling at higher doses) |
| Tmax | ≈2–3 h |
| Half-life | ≈5–7 h |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Not metabolized |
| Excretion | Renal, unchanged (dose adjustment in renal impairment) |
Toxicology & Safety
Not reported
Gabapentin is often perceived as low-risk, and on its own it is relatively safe in overdose, but combined with opioids, benzodiazepines, alcohol or other CNS depressants it significantly raises the risk of sedation, respiratory depression and death. That combination is increasingly seen in overdose fatalities and drove its reclassification as a controlled drug in the UK. It has genuine misuse and dependence potential, especially in people with a history of substance use: regular high-dose use produces tolerance and a withdrawal syndrome, and abrupt discontinuation can provoke seizures, so it must be tapered rather than stopped suddenly. Common effects include dizziness, drowsiness, unsteadiness and peripheral oedema.[3][4]
Legal Status
US: Not federally scheduled. UK: Class C. DE: Prescription only (Rx)
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- Widely prescribed as an anticonvulsant (adjunct for focal seizures) and, most commonly, for neuropathic pain such as postherpetic neuralgia and diabetic neuropathy. Also used off-label for anxiety, restless-legs syndrome and other conditions.
- Increasingly misused recreationally for a mild euphoric, alcohol-like or opioid-potentiating effect: frequently alongside opioids, which is the most dangerous pattern.
- Commonly diverted and misused in prison and opioid-using populations, where its availability and low cost make it a frequent adjunct drug.
Sources & Evidence
- PubChem: Gabapentin (CID 3446) — identifiers & computed properties
- FDA / DailyMed: Gabapentin prescribing information — pharmacokinetics & metabolism
- Yasaei R, Katta S, Patel P, Saadabadi A. Gabapentin. StatPearls [Internet] (NCBI Bookshelf, NBK493228) — pharmacology, medical use & misuse
- Bockbrader HN, Wesche D, Miller R, et al. (2010). A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 49:661-9.
PMID 20818832 · doi:10.2165/11536200-000000000-00000
- Manville RW, Abbott GW (2018). Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels. Mol Pharmacol 94:1155-1163.
PMID 30021858 · doi:10.1124/mol.118.112953
- Gee NS, Brown JP, Dissanayake VU, et al. (1996). The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem 271:5768-76.
PMID 8621444 · doi:10.1074/jbc.271.10.5768
- IUPHAR/BPS Guide to PHARMACOLOGY: gabapentin (ligand 5483) — KCNQ3/KCNQ5 activation data CC BY-SA 4.0
- Wikipedia: Gabapentin (pharmacology, pharmacokinetics, effects & legal status) CC BY-SA 4.0
- PsychonautWiki: Gabapentin — recreational dosage & duration CC BY-SA 4.0
- GOV.UK: Controlled drugs list (Misuse of Drugs legislation) — gabapentin is Class C / Schedule 3 OGL v3.0