4-Methylpregabalin | Wikipedia audio article
Channel: wikipedia tts
Date: 29/10/2018

This is an audio version of the Wikipedia Article:
4-Methylpregabalin

Listening is a more natural way of learning, when compared to reading. Written
language only began at around 3200 BC, but spoken language has existed long ago.

Learning by listening is a great way to:
- increases imagination and understanding
- improves your listening skills
- improves your own spoken accent
- learn while on the move
- reduce eye strain

Now learn the vast amount of general knowledge available on Wikipedia through
audio (audio article). You could even learn subconsciously by playing the audio
while you are sleeping! If you are planning to listen a lot, you could try using
a bone conduction headphone, or a standard speaker instead of an earphone.


You can find other Wikipedia audio articles too at:
https://www.youtube.com/channel/UCuKfABj2eGyjH3ntPxp4YeQ

In case you don't find one that you were looking for, put a comment.
This video uses Google TTS en-US-Standard-D voice.



SUMMARY
=======
4-Methylpregabalin is a drug developed by Pfizer and related to pregabalin, which similarly acts as an analgesic with effectiveness against difficult to treat "atypical" pain syndromes such as neuropathic pain. The effectiveness of pregabalin and its older relative gabapentin against pain syndromes of this kind (which tend to respond poorly to other analgesic drugs) has led to their widespread use, and these drugs have subsequently been found to be useful for many other medical applications, including as anticonvulsants, muscle relaxants, anxiolytics and mood stabilisers.
However these drugs are still of relatively low potency, and scientists have struggled for years to come up with an improvement on pregabalin, with increasing pressure to find a suitably improved replacement before the patent on pregabalin expires in 2018. While it was determined that the mechanism of action involves modulation of the α2δ calcium channel subunits (1 and 2), derivatives that appeared to be more potent and effective than pregabalin at this target when tested in vitro, repeatedly turned out to be weak or inactive when tested in animals. Eventually it was discovered that pregabalin is actively transported across the blood–brain barrier by the system L neutral amino acid transporter protein, which usually functions to transport certain amino acids, including leucine, valine and isoleucine, into the brain.
This explained the previous failures, as most alterations to the pregabalin molecule which increase affinity for the α2δ channels and therefore increase apparent potency in the test tube, were found to also dramatically reduce binding to the system L transporter, and with no assisted transport into the brain, blood–brain barrier penetration was minimal and the drugs were inactive in animals. However, after extensive searching it was discovered that one enantiomer of the relatively simple derivative 4-methylpregabalin, was both 4x higher in binding affinity to α2δ channels than pregabalin, and also retained similar affinity for the system L transporter. This was tested in animals and as hoped, was found to have similar effectiveness to pregabalin as an analgesic and with around 2-3x the potency.It remains unclear at this stage whether (3R,4R)-4-methylpregabalin will now be further developed for medical use in humans however, given the recent development of several competing drugs from the same family which are much further advanced in clinical trials.