Lyrica mechanism of action

Richard Bruce Silverman, a medicinal chemist, developed pregabalin at Northwestern University in the United States and this drug became an approved one in 2004 in the European Union. The Food and Drug Administration (FDA) of the United States approved pregabalin in the latter part of 2004. The FDA approved this drug for treating epilepsy, post herpetic neuralgia and diabetic neuropathy pain. At the fag end of 2005 this drug came to the market. Lyrica was approved by FDA in June 2007 for treating fibromyalgia. Until 2008, in which year duloxetine was approved by FDA for treatment of fibromyalgia, Lyrica was the only approved drug available for treating fibromyalgia.

It is believed that Lyrica (Pregabalin) pacifies the neurons which are in a hyper-excited status. These excited neurons only become the main cause of neurologic pain as experienced in fibromyalgia. Lyrica binds itself strongly with alpha2-delta subunits of calcium channels that are voltage dependent and which are present in the dorsal horn located in the spinal cord and brain too. It is also believed that Lyrica has the capacity of modulating the influx of calcium. This in turn brings down the release of extra neurotransmitters. We can cite here glutamate and substance P as examples. Pregabalin also increases the level of neuronal GABA by increasing glutamic acid decarboxylase. In a single step this enzyme transforms the excited neurotransmitters into inhibitory GABA. This also becomes the main reason for Lyrica to potentiate other depressants. However, Lyrica does not function as a vascular calcium channel blocker. Therefore, vascular functions or cardiac functions are not affected by the working mechanism of Lyrica.

All these hypothetical views kept apart, the clinical significance of Lyrica on humans is not yet clear. At the same time, results of tests on animals suggest that the antinociceptive effects of Lyrica are associated in the above mechanism. May be, in the long run, the mechanism of action of pregabalin becomes very clear, because, this antiepileptic drug is a new one. The special working mechanism of Lyrica contributes well, specifically in the area of diabetic neuropathy. One more interesting fact is that pregabalin is comparable to gabapentin, as far as its structure is concerned. Also, Gabapentin is an antiepileptic drug, and so is pregabalin. Both these drugs have similar site of action, viz. the alpha2-delta protein, which is an auxiliary subunit of calcium channels.

The working mechanism of Lyrica has three stages, namely, absorption, distribution, and metabolism. Excretion takes place ultimately. Lyrica is absorbed quickly when taken on empty stomach. The absorption rate is decreased when taken together with food. However, there is no clinical evidence that the extent of absorption is affected. From the tests with animals it has been observed that pregabalin crosses the blood brain barrier. It also crosses the placenta and its presence in the milk of lactating animals has been observed. In humans, pregabalin undergoes insignificant metabolism. Finally, pregabalin is eliminated as it is from the system by renal excretion.

The action of Lyrica gently reduces the release of varieties of neurotransmitters by binding itself to alpha2-delta subunits. Probably, this is leading to the effect of reduction in the number of the excited neurons. Lyrica's working mechanism also treats seizures. Researches and studies have shown that pregabalin's pharmacology needs binding to alpha-2 delta subunits. The studies also include analyses of certain compounds, which are capable of binding themselves to alpha2-delta subunits, for their structure activity. The findings prior to the clinical trials concur in that Lyrica's mechanism of action reduces abnormal neuronal excitability by reducing the synaptic release of neurotransmitters. However, the site of action, namely the calcium channel alpha2-delta subunit, is only a presumption.