Scan of 27 Million Compounds Identified a New One that Outperforms Pain MedicationsScanning a library of 27 million different molecules, a bi-institutional team identified some that work more effectively than the existing pain medications gabapentin and pregabalin.
Prescribed to nearly 50 million Americans in 2020, gabapentin is used to treat pain and dysfunction related to restless leg syndrome, epilepsy, hot flashes, and neuropathy or nerve pain, while pregabalin is prescribed to nearly 10 million Americans, but has even harsher side effects that can lead to death.
Calcium channels play a central role in pain signaling, in part through the release of neurotransmitters such as glutamate and GABA—“the currency of the pain signal,” according to Rajesh Khanna, director of the NYU Pain Research Center.
The newly identified molecule binds to an inner region of a calcium channel to indirectly regulate it, outperforming gabapentin without troublesome side effects and providing a promising candidate for treating pain.
“Developing effective pain management with minimal side effects is crucial, but creating new therapies has been challenging,” said Khanna, the senior author of the PNAS study which recorded his discovery. “Rather than directly going after known targets for pain relief, our lab is focused on indirectly targeting proteins that are involved in pain.”
In particular, this research centered around a protein called CRMP2, a key regulator of the calcium channel and which binds to it from the inside. He and his colleagues previously discovered a peptide (a small region of amino acids) derived from CRMP2 that could uncouple CRMP2 from the calcium channel.
When this peptide—dubbed the calcium channel‐binding domain 3, or CBD3 (not to be confused with a cannabidiol)—was delivered to cells, it acted as a decoy, blocking CRMP2 from binding to the inside of the calcium channel.
This resulted in less calcium entering the calcium channel and less neurotransmitter release, which translated to less pain in animal studies.....
https://www.goodnewsnetwork.org/scan-of-27-million-compounds-identified-a-new-one-that-outperforms-pain-medications/
