Potential anxiolytics acting via the neuropeptide S-receptor
Neuropeptide S (NPS) represents the latest identified neuropeptide. Animal studies in rodents showed intracerebrally administrated NPS leading to an anxiolytic effect with a simultaneous increase of wakefulness. This activity profile of NPS differs from classical anxiolytic drugs, which cause beside the desired effects also drowsiness. It is therefore of high interest to investigate ligands of the NPS-receptor (NPSR) for their anxiolytic properties and evaluate their potential use as anxiolytic drugs. One promising strategy in the search for novel bioactive compounds is the use of virtual screening tools, which can effectively reduce cost and time efforts. This approach resulted in the first pharmacophore modeling study on NPSR ligands. Since the 3D structure of the G-protein coupled NPSR is not known, ligand-based pharmacophore models were generated. The theoretical model evaluation by two test sets containing non-peptidic active compounds and presumably inactive decoys revealed enrichment factors and ROC curves, which indicate a good predictive power of the generated models and will contribute to the rationalized search for novel NPSR ligands. The virtual screening of natural product databases led to promising structures in regard to traditional used plants.