Description of Gabapentin
|Common names||Gabapentin, Neurontin, Gabarone, Gralise|
|Systematic name||1-(Aminomethyl)cyclohexaneacetic acid|
gabapentin (also known as neurontin) is a depressant substance of the gabapentinoid class which is used as an anticonvulsant, analgesic and anxiolytic. it was originally developed to treat epilepsy and is currently used to relieve neuropathic pain and restless leg syndrome. it is recommended as a first line agent for the treatment of neuropathic pain arising from diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain.
gabapentin is also an effective tool for treating social anxiety disorder, panic disorder and generalized anxiety disorder. it is these effects which provide the recreational potential in a manner that can be accurately compared to a mild benzodiazepine. however, these recreational effects diminish very quickly with repeated usage and are most commonly reported by those who do not have a tolerance to this compound.
Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter gaba. it contains a cyclohexane ring bound to a methylamino chain ch3nh2. at the same location, r1, the cyclohexane ring is also substituted with an acetic acid group. It is structurally analagous to gaba. gaba contains an amino group bound to the terminal carbon of a butanoic acid chain. the structure of this compound contains the secondary carbon r3 of the butanoic acid chain in gaba incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.
Gabapentin modulates the action of glutamate decarboxylase (gad) and branched chain aminotransferase (bcat), two enzymes involved in gaba biosynthesis. in human and rat studies, it was found to increase GABA-A biosynthesis, and to increase non-synaptic GABA neurotransmission in vitro. as the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the sedating and anxiolytic (or calming effects) of gabapentin on the nervous system.
It has also been shown to bind to the α2δ-1 subunit of voltage-gated calcium channels to act as a vgcc blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. it is uncertain exactly how this method of action contributes to it’s psychoactive effects.
the bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower biovailability than lower doses). the bioavailability is approximately 60%, 47%,
34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day. It is highly Lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. this means that eating a high fat meal substantially increases it’s bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase compound absorption by decreasing “gabapentin transporter” saturation.
transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.