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Gabapentin

Gabapentin Mechanism of Action

Gabapentin was designed to mimic the neurotransmitter GABA.

It does not, however, bind to GABA receptors. Its mechanism of action as an antiepileptic agent likely involves its inhibition of the alpha 2-delta subunit of voltage-gated calcium channels .

It was first approved as an anticonvulsant in 1994 in the US and is now available worldwide.  It was also approved in the US for postherpetic neuralgia in 2002 and is used commonly to treat neuropathic pain. Gabapentin is renally excreted and is not an enzyme-inducing anticonvulsant.

Gabapentin use resulted in increased fracture in the Canadian population-based study . There is limited study on effects of gabapentin on BMD. Several studies have evaluated adults taking anticonvulsant that included gabapentin. These data suggest that gabapentin may cause bone loss.

Gabapentin (Generic Neurontin ) is used to help control partial seizures (convulsions) in the treatment of epilepsy. This medicine cannot cure epilepsy and will only work to control seizures for as long as you continue to take it.

Gabapentin (Generic Neurontin ) is also used to manage a condition called postherpetic neuralgia, which is pain that occurs after shingles. It’s also taken for nerve pain. Nerve pain can be caused by different illnesses, including diabetes and shingles, or it can happen after an injury.

Gabapentin (Generic Neurontin ) works in the brain to prevent seizures and relieve pain for certain conditions in the nervous system. It is not used for routine pain caused by minor injuries or arthritis. Gabapentin is an anticonvulsant.

Occasionally, gabapentin (Generic Neurontin ) is used to prevent migraine headaches. Gabapentin (Neurontin) and pregabalin (Lyrica) are anticonvulsants and nerve pain medicines which have structural similarities to the inhibitory neurotransmitter GABA.

Gabapentin (Generic Neurontin ) is available only with your doctor’s prescription.

Gabapentin (Generic Neurontin ) is available in the following dosage forms:
Capsule
Tablet
Tablet, Extended Release, 24 HR
Solution
Suspension

Gabapentin (Generic Neurontin ) was developed in 1993 and has indications for shingles (‘postherpetic neuralgia’) and partial-onset seizures. It has had a growing popularity in off-label uses for fibromyalgia, pain from a variety of causes, migraine, cocaine withdrawal, anxiety, and insomnia. A related compound, gabapentin encarbil (Horizant), is approved for shingles and restless leg syndrome. Pregabalin was developed in 2004 and is approved for nerve pain from diabetes and spinal cord injuries, fibromyalgia, and adjunctive treatment of partial-onset seizures. Although prescribed off-label for anxiety in the U.S., it is approved for this purpose in the U.K., where it is sometimes called the ‘new Valium’.

The previously described MrOS study found significant bone loss at the hip in older men prescribed gabapentin . There are no reports evaluating whether gabapentin treatment results in changes in markers of bone and mineral metabolism.

Future studies should focus on whether gabapentin, which is commonly used for multiple indications, adversely affects bone.

Gabapentin and pregabalin are structurally related compounds with recognized efficacy in the treatment of both epilepsy and neuropathic pain. The pharmacological mechanisms by which these agents exert their clinical effects have, until recently, remained unclear.

The interaction of gabapentin and pregabalin with conventional antiepileptic and analgesic drug targets is likely to be modest, at best, and has been largely dismissed in favour of a selective inhibitory effect on voltage-gated calcium channels containing the alpha2delta-1 subunit.

This mechanism is consistently observed in both rodent- and human-based experimental paradigms and may be sufficiently robust to account for much of the clinical activity of these compounds.

The chemical structure of gabapentin (Neurontin) is derived by addition of a cyclohexyl group to the backbone of gamma-aminobutyric acid (GABA). Gabapentin prevents seizures in a wide variety of models in animals, including generalized tonic-clonic and partial seizures.

Gabapentin has no activity at GABAA or GABAB receptors of GABA uptake carriers of brain. Gabapentin interacts with a high-affinity binding site in brain membranes, which has recently been identified as an auxiliary subunit of voltage-sensitive Ca2+ channels.

However, the functional correlate of gabapentin binding is unclear and remains under study. Gabapentin crosses several lipid membrane barriers via system L amino acid transporters. In vitro, gabapentin modulates the action of the GABA synthetic enzyme, glutamic acid decarboxylase (GAD) and the glutamate synthesizing enzyme, branched-chain amino acid transaminase.

Results with human and rat brain NMR spectroscopy indicate that gabapentin increases GABA synthesis. Gabapentin increases non-synaptic GABA responses from neuronal tissues in vitro. In vitro, gabapentin reduces the release of several mono-amine neurotransmitters.

Gabapentin prevents pain responses in several animal models of hyperalgesia and prevents neuronal death in vitro and in vivo with models of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Gabapentin is also active in models that detect anxiolytic activity.

Although gabapentin may have several different pharmacological actions, it appears that modulation of GABA synthesis and glutamate synthesis may be important.