Questions from membership
Answers from Kevin T. Sperber, MD
Vice Chairman of the Department of Rehabilitation Medicine
North Bronx Healthcare Network

***Please note that these are general answers and are not specific to your individual case.
See your own specialist with any concerns.***

Question: My medication was recently switched from Neurontin to Lyrica. My pain is being managed and I feel a lot better. How does Lyrica work? And how is it different than Gabapentin?

Dr Sperber: The mechanism of action for both Neurontin (gabapentin) and Lyrica (pregablin) is poorly understood. There is an important neuro transmitter in the brain called GABA  and both these medications have structural similarities to GABA. However, they work on slightly different receptors in the brain. For a more technical discussion of the mechanism of both these medications I will paraphrase the reference Micromedex 2.0

“Pregabalin is a GABA analog that strongly binds to the alpha(2)-delta site (a subunit of voltage-gated calcium channels) in central nervous system tissues. Binding to the alpha(2)-delta subunit may be involved in pregabalin's effects on neuropathic pain and seizure control. Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function, however the exact mechanism of action is unknown”

“Gabapentin is structurally related to the neurotransmitter GABA; however, gabapentin and its metabolites do not bind to GABA (A) or GABA (B) receptors or influence the degradation or uptake of GABA it has been suggested the mechanism of action may be by gabapentin preventing thrombospondin from binding to alpha 2 delta-1 “

In summary, we don’t quite know how they work. However, they do seem to have similar effects on nerve related pain. However, tolerability and effectiveness can vary ignorantly among individuals and if someone finds one ineffective the other is still worth trying.

Question:  Is there such a point where a pain medication, Neurontin, is at the highest level possible for effectiveness?  I am on 3400 mg/day and different strengths are spread throughout the day.  Is it possible to develop a tolerance so that the effectiveness becomes lessened?

Dr Sperber: The bioavability (the amount in the bloodstream) of both Neurontin (gabapentin) decreases with increasing dose, so increasing the dose may not have a significant impact. The effective dose can vary significantly between individuals so it generally needs to be titrated,  based on it’s effect. With any medication there can be tachyphalaxis  (decreased effectiveness of medication overtime with use) can develop but, is not frequently reported with gabapentin.

DOSAGE ORAL

(3 divided Doses) BIOAVAILABILITY

900 milligrams 60%

1200 milligrams 47%

2400 milligrams 34%

3600 milligrams 33%

4800 milligrams 27%

(Prod info Neauronlin(R), 2002)

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