Gabapentin, brand name Neurontin, was developed by Parkes-Davis, a division of Warner-Lambert, which was acquired by Pfizer in 2000. 

Description

Gabapentin is sold solely by Pfizer, Inc. (http://www.pfizer.com) under the brand name Neurontin. It comes in hard-shell capsules in 100, 300, and 400mg doses, in elliptical film-coated tablets of 600 and 800mg, and in an oral solution containing 250 mg/mL of gabapentin.

Indications

Gabapentin is FDA approved for use in treating post-herpetic neuralgia (pain related to shingles) and as an adjunct therapy for epilepsy. Common off-label uses include:

opain of all types

o    biopolar disorder

omigraine headaches

otremors related to Parkinson’s Disease and Lou Gherig’s Disease

oanxiety

oschizophrenia

Of these off-label uses, Neurontin has only been proven to work consistently in treating neuropathic (nerve) pain. It has actually made many patients with bipolar disorder and schizophrenia more violent, however; it does work for some patients. Those who fear the side effects of medications traditionally used to treat these disorders often prefer to try Neurontin first because of its relatively mild side effects.

Physiology

GABA and Epilepsy

GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the central nervous system. Because excessive excitation can lead to seizures, malfunctioning GABAergic neurons and pathways are thought to be one of the primary causes of epilepsy.

GABA and Neuropathic (Nerve) Pain

Neuropathic pain is usually described as "burning", "electric", "tingling", and "shooting" in nature. This pain is usually caused by damage or change in the either the peripheral or central nervous system, causing the nerve fibers to send pain signals when there is no appropriate stimulus, or to send stronger pain signals than is appropriate to the stimulus. Because of GABA’s inhibitory effects, many drugs that affect or mimic GABA are useful in treating neuropathic pain.

Gabapentin

Gabapentin is described as 1-(aminomethly)cyclohexaneacetic acid. It is structurally similar to the neurotransmitter GABA (gamma-aminobutyric acid), but doesn’t bind directly to GABA receptors in the brain. Instead, it increases GABA levels by affecting a transporter protein. It also decreases the activity of voltage-gated calcium channels by binding to a secondary protein. The exact mechanisms of both these actions are not known.According to neurologist Brian Loftus, “This effect occurs in only some of the neurons depending on additional cofactors being present (mechanism not clearly understood). It is therefore possible that this medication in some way targets abnormally acting neurons and not the normal neurons.”

An interesting characteristic of this drug is that its bioavailability is not proportional to the dose. As the dose is increased, the bioavailability decreases, and any doses larger than 4800 mg per day, many patients stop absorbing the additional dose. Food has only a small effect on the rate and extent of absorption. Also, Gabapentin is not noticeably metabolized in the human body; it is excreted in urine in an unchanged state. For both of these reasons, Gabapentin is seen as a “safer” drug than many others used to treat the same symptoms.

Warnings and Side Effects

Common side effects are:

odizziness

odrowsiness

odry mouth

oconstipation

oindigestion, gas, or heartburn

onausea

oloss of appetite

oincrease in apptetite

Less common side effects are:

oataxia (muscle coordination problems)

oback pain, joint aches and pains

opain, burning, or tingling in hands or feet

orestlessness

osexual difficulty

oskin itching

oslurred speech sore gums

otremor

oweight gain

Children aged 3-12 years may experience:

ofever

ohyperactivity

ohostile or aggressive behavior

omood changes or changes in behavior

odifficulty concentrating

Contraindications

People who have had past allergic reactions to this drug should not take Gabapentin.

People with kidney disease or low kidney function should consult a doctor before taking this medication.

Drug Interactions

Tagemet (cimetidine) – Gabapentin will not be excreted from the body as effectively if taken in conjunction with this medication.

Antacids should not be taken within two hours of taking a dose of Gabapentin.

References and Resources

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Full prescribing information for Neurontin:

http://www.pfizer.com/do/medicines/mn_neurontin.html

from Pfizer, Inc.

An in-depth explanation of GABA and GABA receptors.

http://www.biotrend.com/pdf/gabarev.pdf

from BioTrend (biochemical supplier)

A paper on the effects of alcohol on the GABAA receptor. Includes a good explanation of one of the ways GABA affects the nervous system.

http://www.niaaa.nih.gov/publications/arh21-2/127.pdf

from the National Institute of Health

A paper on GABAA receptor defects and their role in epilepsy.

http://www.aesnet.org/currents_pdf/EPCreceptor.pdf

from the American Epilepsy Society

A paper on the causes and treatments of neuropathic pain.

http://www.spineuniverse.com/displayarticle.php/article1614.html

from Spine Universe (internet portal for health professionals and patients)

A paper on the use of Gabapentin to treat bipolar disorder. Requires free registration.

http://www.medscape.com/viewarticle/417970

from MedScape (divison of WebMD.com)