Gabapentin

1 - ( aminomethyl) - cyclohexylacetic

• C9H17NO2 ( gabapentin )
• C9H17NO2 · HCl ( gabapentin hydrochloride)

• 60142-96-3 ( gabapentin )
• 60142-95-2 ( gabapentin hydrochloride)

N03AX12

Antiepileptic

162-166 ° C and 165-167 ° C

Risk

Template: Infobox chemical / molecular formula search available

Gabapentin is a pharmaceutical from the group consisting of anticonvulsant, which is used for the treatment of epilepsy and neuropathic pain. The drug was patented by Goedecke and Warner -Lambert in 1976.

Pharmacology

Areas of application

Gabapentin is approved for monotherapy of simple and complex partial seizures with or without secondary generalization and adjunctive therapy of partial seizures with and without secondary generalization. A further indication is the treatment of neuropathic pain. Neuropathic pain is caused, for example, in a subset of patients with shingles after resolution of lesions, post - herpetic neuralgia. Another common application is the diabetic neuropathy and the treatment of phantom pain. Also, postoperative pain can be alleviated by gabapentin. The substance can also be effective in refractory cough, when the cause does not require other measures.

As part of " off-label " ( ie, outside of the approved in the authorization usage ) it can be used in multiple sclerosis and spasticity when no adequate relief could be achieved with the approved substances with adequate dosage and duration or intolerance to. A decision of the Federal Joint Committee (G -BA ) for the regulation ability in non-approved application is entered into force in March 2014.

Mechanism of Action

The mechanism of action of gabapentin is not yet fully understood. Its anti-convulsant activity is not brought to direct activation of GABA A receptors in connection, although it is structurally related to GABA. As a mechanism of inhibition of glutamatergic synaptic transmission and the central blockade of calcium channels (N, P / Q) is discussed.

Side effects (excerpt)

The most common side effects during use of Gabapentin are pronounced dry mouth, fatigue, dizziness, headache, nausea, vomiting, weight gain, nervousness, insomnia, ataxia, nystagmus, paresthesia, increased appetite, but also loss of appetite and anorexia. In addition, middle ear infection, viral and respiratory infections, leuco - and thrombocytopenia, mental disorders such as anxiety, depression, hallucinations, thought disorder, hostility, amnesia and confusion occur.

Interactions

The absorption of gabapentin can be influenced by concomitant intake of calcium - or magnesium-containing antacids. Morphine and alcohol can increase the effects and side effects of gabapentin.

Gabapentin may influence the outcome of some urine tests false positive on protein.

Administration

The drug is taken orally, the drug remains at a half-life of 5 to 7 hours in the blood. Eliminated it is via the urine.

Physical and Chemical Properties

Gabapentin is an analog of γ -aminobutyric acid ( GABA). It is present predominantly as the "inner salt " or zwitterion, whose formation can be explained by the fact that the proton of the carboxyl group migrates to the lone pair of the nitrogen atom of the amino group.

Zwitterion form of gabapentin

In an electric field, the zwitterion migrates not because it is not loaded as a whole. Strictly speaking, this is at the isoelectric point ( at a certain pH value) of the case in which the gabapentin has its lowest solubility in water.

The compound tends to be intramolecular lactam. As an impurity due to the production or storage of the lactam in the pharmaceutical product should be avoided since this may be more toxic than gabapentin.

Synthesis

Gabapentin can be made in three reaction steps from 2- Cyclohexylidenmalonsäurediethylester. In this case, first by reaction with cyanide of the 2- cyclohexyl-2- cyanomalonsäurediethylester. A subsequent reductive cyclization results in a Lactamzwischenverbindung which is boiled under acidic conditions to gabapentin.

Trade names

Gababurg (A), Gabagamma (D), GabaLich (D), Gabalster (A), Gabatal (A), Gabantin (CH), Gabax (D), Neurontin (D, A, CH ), numerous generics (D, A, CH )