Alpidem

Anxiety disorders are the most prevalent psychiatric pathology with substantial cost to society, but the existing treatments are often inadequate. This has rekindled the interest in the GABA_A-receptor (GABA_AR) positive allosteric modulator (PAM) compounds, which have a long history in treatment of anxiety beginning with diazepam, chlordiazepoxide, and alprazolam. While the GABA_AR PAMs possess remarkable anxiolytic efficacy, they have fallen out of favor due to a host of adverse effects including sedation, motor impairment, addictive potential and tolerance development. A substantial effort was thus devoted to the design of GABA_AR PAMs as anxiolytics with reduced sedative liabilities. Several non-benzodiazepine (BZD) GABA_APAMs progressed to clinical trials (bretazenil, abecarnil, alpidem, and ocinaplon) with alpidem obtaining regulatory approval as anxiolytic, but later withdrawn from market due to hepatotoxicity. Advances in molecular biology gave birth to a host of subtype selective GABA_AR-PAMs which suffered from signs of sedation and motor impairment and only three compounds progressed to proof-of-concept studies (TPA-023, AZD7325 and PF-06372865). TPA-023 was terminated due to toxicity in preclinical species while AZD7325 and PF-06372865 did not achieve efficacy endpoints in patients. We highlight a new compound, KRM-II-81, that is an imidazodiazepine selective for GABA_AR containing α2/3 and β3 proteins. In preclinical studies KRM-II-81 produced anxiolytic-like effects but with minimal sedation, respiratory depression, and abuse liability. Thus, KRM-II-81 is a newly discovered, non- BZD anxiolytic compound, which targets a selective population of GABA_AR for improved therapeutic gain and reduced side effects.

Regarding scientific research, Imidazo[1,2-a] pyridine derivatives are constantly being developed due to the scaffold’s intriguing chemical structure and varied bio-logical activity. They are distinctive organic nitrogen-bridged heterocyclic compounds that have several uses in medicines, organometallics and natural products. It has become a vital tool for medicinal chemists.

In order to gather scientific information on Imidazo[1,2-a] pyridines derivative, Google, PubMed, Scopus, Google Scholar, and other databases were searched. In the current study, the medicinal value and therapeutic effect of Imidazo[1,2-a] pyridines were investigated using above mentioned databases. The current study analyzed the detailed pharmacological ac-tivities of Imidazo[1,2-a] pyridine analogs through literature from diverse scientific research works.

Due to its wide range of biological activities, including antiulcer, anticonvulsant, anti-protozoal, anthelmintic, antiepileptic, antifungal, antibacterial, analgesic, antiviral, anticancer, anti-inflammatory, antituberculosis, and antitumor properties, imidazopyridine is one of the most significant structural skeletons in the field of natural and pharmaceutical products. An imidazopyridine scaffold serves as the basis for a number of therapeutically utilized medica-tions, including zolpidem, alpidem, olprinone, zolimidine, and necopidem.

This comprehensive study covers the period of the last five years, and it sheds light on the developments and emerging pharmacological actions of Imidazo[1,2-a] pyridines. Additionally, the structure-activity relationship and molecular docking studies are carefully documented throughout the paper, providing medicinal chemists with a clear picture for devel-oping new drugs.