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New drug VIP36 shows promise in treating pain without harmful side effects

March 5, 2025
in Health
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A analysis staff funded by the Nationwide Institutes of Well being (NIH) has developed a drugs that reveals promise in treating acute and power ache. The drug, referred to as VIP36, targets the physique’s cannabinoid receptor sort 1 (CB1). It was discovered to be efficient in three totally different animal fashions for ache and doesn’t seem to trigger the dangerous uncomfortable side effects which have annoyed different efforts to focus on CB1. These outcomes improve understanding of tips on how to design safer and more practical medicine focusing on cannabinoid receptors and are an essential step in direction of creating novel, non-addictive therapies for ache.

CB1 receptors will be discovered all through the physique and are significantly dense within the mind’s ache circuitry. They’ve lengthy been thought of a possible goal for non-opioid-based ache remedy; nevertheless, earlier makes an attempt to focus on this pathway have been met with two challenges. First, repeated publicity to a drug results in tolerance that limits its efficacy. Second, the dose required to scale back ache within the periphery tends to be excessive sufficient for the drug to make its manner into the central nervous system. In people, this may trigger undesirable modifications in temper, cognition, or emotional state.

To beat these points, researchers leveraged laptop modeling of the CB1 receptor to design molecules that higher work together with CB1, very similar to a key becoming right into a lock.  The newly designed drug, VIP36, is extra “peripherally restricted” in comparison with earlier medicine, that means that a lot much less of it leaks into the central nervous system the place it could possibly trigger undesirable uncomfortable side effects. VIP36 additionally interacts with CB1 in a different way than therapies examined beforehand and in a manner that reduces tolerance.

CB1 is a part of a wide-ranging class of receptors referred to as G-protein-coupled receptors, that are concerned in numerous features all through the physique together with scent, imaginative and prescient, temper regulation, immune system responses, autonomic nervous system responses corresponding to blood strain and coronary heart charge, and progress and metastasis of some tumors. Along with their implications in ache care, the findings of this research might additionally assist spur the design of different medicine that focus on related receptors concerned in different circumstances.

This analysis was funded by NIH’s Serving to to Finish Habit Lengthy-term® Initiative, or NIH HEAL Initiative®, an NIH-wide effort that seeks to hurry scientific options to the overdose epidemic, together with opioid and stimulant use issues, and the disaster of power ache.

Supply:

Nationwide Institutes of Well being

Journal reference:

Rangari, V. A., et al. (2025) A cryptic pocket in CB1 drives peripheral and practical selectivity. Nature. doi.org/10.1038/s41586-025-08618-7.



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