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The mechanism of action of Neurontin

Posted by PaulB on August 27, 2001, at 15:02:13

I thought some psycho-babblers would be interested in the mechanism by which Neurontin and the newer analogue Pregablin exert their anticonvulsant and anxiolytic effect.

Prior to some recent information I have disocovered the way in which Neurontin works. Although both Neurontin and Pregabalin are structurally related to GABA neither interact with GABA receptors. I think sometimes the fact that Neurontin is an analogue, structurally of the neurotransmitter GABA has meant that its mechanism of action has been misinterpreted. That some people believe that it simply mimics the activity of the neurotransmitter. This is not true.

There seems to be very, very little information on the real mechanism of action of Neurontin probably because our understanding of these two drugs is really only beginning but I recently came across a fascinating article which did show Neurontins mechanism of action:

http://www.brjpharmacol.org/cgi/content/full/132/1/1

This abstract I downloaded at medline and is a very recent article, focuses more on Pregabalin than Neurontin but the authors indicate that they work via the same mechanism. The article explains how Pregabalin binds with high affinity and selectivity to a subunit of voltage dependant calcium channels(VDCC). These channels may play an importnat role in neurotransmitter release, and perhaps Neurontin works by its ability to stimulate the release of neurotransmitters, perhaps foremost GABA. I myself have been given a trial of Neurontin and noticed a stimulant effect. This, I believe is not uncommon. Perhaps the binding to this particular calcium channel stimulates the release of other neurotransmitters which explains this. I hope the link above works. I have tested it.
PaulB


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