Gabapentin EU

Gabapentin is a synthetic analog of gamma-aminobutyric acid (GABA), originally developed as an antiepileptic drug (AED). Though structurally related to GABA, gabapentin does not bind to GABA receptors; instead, it modulates voltage-gated calcium channels by binding to the α2δ subunit. This results in decreased excitatory neurotransmitter release, making it effective in a range of neurological and psychiatric disorders.

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Chemical Information

• IUPAC Name: 1-(aminomethyl)cyclohexaneacetic acid
• Molecular Formula: C9H17NO2
• Poids moléculaire: 171.24 g/mol
• CAS Number: 60142-96-3
• Drug Class: Anticonvulsant, Neuromodulator

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Pharmacodynamie

Gabapentin does not directly modulate GABA receptors but exerts its effects by binding with high affinity to the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels (VGCCs). This leads to:

• Reduced calcium influx in neurons
• Inhibition of excitatory neurotransmitters like glutamate and substance P
• Modulation of pain signaling in the spinal cord

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Indications

Gabapentin is approved or widely used off-label for:

• Epilepsy (partial seizures, adjunct therapy)
• Neuropathic pain (postherpetic neuralgia, diabetic neuropathy)
• Generalized anxiety disorder (off-label)
• Fibromyalgie
• Alcohol withdrawal syndrome
• Restless Legs Syndrome (off-label)

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Dosage et administration

Typical adult dosages vary by condition:

• Epilepsie: 900–1800 mg/day, in 3 divided doses
• Douleur neuropathique: Start at 300 mg once daily, titrate to 1800–3600 mg/day
• Anxiety (off-label): 300–1200 mg/day

Titration is critical to minimize side effects, and abrupt discontinuation should be avoided to prevent withdrawal symptoms or seizure rebound.

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Pharmacocinétique

• Absorption: Bioavailability is dose-dependent (60% at 300 mg, drops with higher doses)
• Distribution: Not significantly protein-bound; crosses the blood-brain barrier
• Métabolisme: Not metabolized by the liver
• Excrétion: Renal elimination; unchanged
• Half-life: ~5–7 hours

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Effets secondaires

Commun :

• Somnolence
• Vertiges
• Ataxia
• Fatigue
• Peripheral edema

Rare:

• Mood changes
• Suicidal ideation
• Severe allergic reactions (DRESS syndrome)

Gabapentin may cause dependence in some individuals, especially at high doses or with long-term use. Caution is advised in individuals with a history of substance misuse.

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Harm Reduction & Safety

• Avoid combining with other CNS depressants (e.g., alcohol, benzodiazepines)
• Renal function should be assessed regularly in chronic users
• Tapering is necessary to avoid withdrawal symptoms
• May impair cognitive and motor skills—caution with driving or machinery

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Legal Status

• ÉTATS-UNIS: Prescription-only, Schedule V in some states due to abuse potential
• L'UE: Prescription-only, not scheduled
• ROYAUME-UNI: Controlled (Class C, Schedule 3) due to rising misuse

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Research and Emerging Uses

Gabapentin continues to be studied in:

• Chronic cough
• Migraine prophylaxis
• Social anxiety disorder
• PTSD-related sleep disturbances

Its role in modulating central sensitization makes it a candidate in multiple pain-related and psychiatric conditions.

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Conclusion

Gabapentin is a well-established neuromodulatory agent with a broad therapeutic range. Despite its relatively benign profile, responsible use and harm reduction are essential due to potential misuse and withdrawal risks. For researchers, it offers a powerful tool for studying calcium channel modulation and neuropathic pathways.