AI Article Synopsis
- - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide linked to emotional stress and anxiety disorders, prompting research into its receptor antagonists.
- - Small-molecule PACAP receptor antagonists, specifically PA-9 and PA-915, showed promise in reducing anxiety-like behaviors in mice during acute restraint stress.
- - PA-915 was notably effective in this role, outperforming fluoxetine, highlighting its potential as a new anxiety treatment.
Article Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.
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| http://dx.doi.org/10.1016/j.bbrc.2022.09.079 | DOI Listing |
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