2994
T3D2952
Gabapentin
Gabapentin was originally developed as a chemical analogue of gamma-aminobutyric acid (GABA) to reduce the spinal reflex for the treatment of spasticity and was found to have anticonvulsant activity in various seizure models. In addition, it also displays antinociceptive activity in various animal pain models. Clinically, gabapentin is indicated as an add-on medication for the treatment of partial seizures, and neuropathic pain. It was also claimed to be beneficial in several other clinical disorders such as anxiety, bipolar disorder, and hot flashes. The possible mechanisms or targets involved in the multiple therapeutic actions of gabapentin have been actively studied. Since gabapentin was developed, several hypotheses had been proposed for its action mechanisms. They include selectively activating the heterodimeric GABA(B) receptors consisting of GABA(B1a) and GABA(B2) subunits, selectively enhancing the NMDA current at GABAergic interneurons, or blocking AMPA-receptor-mediated transmission in the spinal cord, binding to the L-alpha-amino acid transporter, activating ATP-sensitive K(+) channels, activating hyperpolarization-activated cation channels, and modulating Ca(2+) current by selectively binding to the specific binding site of [(3)H]gabapentin, the alpha(2)delta subunit of voltage-dependent Ca(2+) channels. Different mechanisms might be involved in different therapeutic actions of gabapentin. In this review, we summarized the recent progress in the findings proposed for the antinociceptive action mechanisms of gabapentin and suggest that the alpha(2)delta subunit of spinal N-type Ca(2+) channels is very likely the analgesic action target of gabapentin. (A7831).
60142-96-3
3446
C9H17NO2
171.125930
White powder.
162-166°C
4490 mg/L
Oral. Rapid. Absorbed in part by the L-amino acid transport system, which is a carrier-mediated, saturable transport system; as 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).
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.
All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans.
Route of Elimination: Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug.
Gabapentin is not appreciably metabolized in humans.
Half Life: 5-7 hours
LD50: >8000 mg/kg (oral,rat) [MSDS]
LD50: 8053 mg/kg (oral, mouse) [MSDS]
No indication of carcinogenicity to humans (not listed by IARC).
It was originally developed for the treatment of epilepsy, and currently, gabapentin is widely used to relieve pain, especially neuropathic pain. [wikipedia]. For the management of postherpetic neuralgia in adults and as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy.
May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation.
Gabapentin can be removed by hemodialysis. (L1712)
2009-07-21T20:28:07Z
2014-12-24T20:25:54Z
Gabapentin
42797
Gabapentin
DB00996
GBN
true
NCC1(CC(O)=O)CCCCC1
C9H17NO2
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
171.2368
171.125928793
Exogenous
Solid
-1.1
HMDB05015
CHEMBL940
3328
<p>Donald E. Butler, Barbara J. Greenman, “Gabapentin mohohydrate and a process for producing the same.” U.S. Patent US4960931, issued May, 1978.</p>