4-Methylpregabalin is a drug developed by Pfizer and associated with pregabalin, which also acts as an analgesic with effectiveness against the difficulty of treating "atypical" pain syndromes such as neuropathic pain. The relatively older pregabalin and gabapentin effectiveness of this type of pain syndrome (which tends to respond poorly to other analgesic drugs) has led to its widespread use, and these drugs are found to be useful for many other medical applications, including anticonvulsants, muscle relaxants, anxiolytics and mood stabilizers.
But these drugs still have relatively low potential, and scientists have struggled for years to produce improvements to pregabalin, with increasing pressure to find the right replacement before the pregabalin patent ends in 2018. While it is determined that the mechanism of action involves the modulation of? 2 ? calcium channel subunits (1 and 2), a derivative that appears to be stronger and more effective than pregabalin in this target when tested in vitro, repeatedly turns out to be weak or inactive when tested in animals. Finally it was found that pregabalin is actively transported across the blood-brain barrier by the L-amino acid binding protein, which normally serves to transport certain amino acids, including leucine, valine and isoleucine, to the brain.
This explains the previous failure, since most of the changes to the pregabalin molecules that increase the affinity for? 2 ? channel and therefore increase the apparent potential in the test tube, was also found to dramatically reduce the binding of the L system transporter, and without the aid of transport to the brain, the penetration of the blood-brain barrier was minimal and the drugs inactive in animals. However, after extensive searches it was found that one enantiomer of a relatively simple 4-methylpregabalin derivative, is it 4x higher in binding affinity to? 2 ? channels of pregabalin, and also maintaining the same affinity for L system transporters. It was tested on animals and as expected, was found to have the same effectiveness as pregabalin as an analgesic and with about 2-3x potential.
It remains unclear at this stage whether (3 R , 4 R ) - 4-methylpregabalin will now be further developed for medical use in humans, however, given the recent developments of some competing drugs from the same family that are much more advanced in clinical trials.
Video 4-Methylpregabalin
See also
- Atagabalin
- Gabapentin enacarbil
- PD-217,014
Maps 4-Methylpregabalin
References
Source of the article : Wikipedia
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