Agonists and antagonists of the orexinergic system: therapeutic molecules of the future - a narrative review

<p>The orexinergic system involves orexin (OX) neurons, OX peptides, and OX receptors. OX neurons are located throughout the central nervous tissue (including many nuclei) and the peripheral nervous tissue and organs. These neurons are critically involved in the sleepwake transition, cardiorespiratory, and autonomic regulations. OX antagonists include selective OX type 1 receptor (OX1R) antagonists, selective OX type 2 receptor (OX2R) antagonists, and dual OX1/2R antagonists. Similarly, OX agonists include dual OX1/2R agonists and selective OX1R or OX2R agonists. Recent understandings of the therapeutic mechanism of OX have led to possible therapeutic options in diseases such as insomnia, narcolepsy, psychiatric disorders, and neurodegenerative diseases. This review focuses on the therapeutic roles of OXs as agonists or antagonists in animal models and human patients, which can lead to possible avenues related to their application in health and disease.</p>