July 20, 2024
Compound Demonstrates Superiority Over Pain Drug by Indirectly Targeting Calcium Channels

Compound Demonstrates Superiority Over Pain Drug by Indirectly Targeting Calcium Channels

A new compound has been discovered that outperforms a commonly used pain medication by indirectly regulating calcium channels. The study, led by the NYU College of Dentistry’s Pain Research Center, found that the compound reversed four types of chronic pain in animal studies. The research, published in the Proceedings of the National Academy of Sciences (PNAS), suggests that this small molecule holds promise as a potential treatment for pain.

Calcium channels play a crucial role in pain signaling, releasing neurotransmitters like glutamate and GABA that contribute to the pain signal. Current drugs for pain relief, such as gabapentin and pregabalin, target the Cav2.2 calcium channel. However, these medications often come with unwanted side effects.

The compound discovered in this study binds to an inner region of the calcium channel, effectively regulating its activity. Unlike gabapentin, the new compound showed better efficacy in relieving pain and did not produce any undesirable side effects.

Dr. Rajesh Khanna, director of the NYU Pain Research Center and the senior author of the study, explained that their approach focused on indirectly targeting proteins involved in pain, rather than directly going after known pain relief targets. Their research had previously identified a peptide derived from a protein called CRMP2 that could block the protein from binding to the calcium channel when delivered to cells. This resulted in reduced calcium influx and decreased neurotransmitter release, ultimately leading to less pain in animal studies.

To overcome the limitations of using peptides as drugs due to their short duration of action and vulnerability to degradation in the stomach, the researchers attempted to create a small molecule drug based on the CRMP2-derived peptide. Through a computer simulation and experimental testing, they identified a compound called CBD3063 as the most promising candidate for pain treatment. CBD3063 disrupted the interaction between the calcium channel and CRMP2 protein, reducing calcium influx and neurotransmitter release.

Further studies conducted in collaboration with researchers at various universities confirmed the efficacy of CBD3063 in relieving different types of chronic pain, including chemotherapy-induced neuropathy, inflammatory pain, and trigeminal nerve pain. Additionally, compared to gabapentin, CBD3063 required much lower doses to achieve pain reduction.

Dr. Khanna highlighted that their unique approach of targeting the inner region of the calcium channel may be the key to their success. By indirectly regulating calcium channels, the compound offers a novel mechanism of action for pain relief. Furthermore, CBD3063 demonstrated superior efficacy over gabapentin without causing sedation, cognitive changes, or alterations in heart rate and breathing.

This research provides promising preclinical evidence for the development of a new pain medication with improved effectiveness and fewer side effects. However, further studies, including clinical trials, are necessary to determine the full potential of this compound as a pain treatment option.

1. Source: Coherent Market Insights, Public sources, Desk research
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