Non-peptidic natural products that target and modulate oxytocin and arginine vasopressin receptors: Opportunities and challenges

J Pharmacol Sci. 2025 Jul;158(3):238-258. doi: 10.1016/j.jphs.2025.04.004. Epub 2025 Apr 14.

Abstract

The ability to target the oxytocin and vasopressin receptors is of high therapeutic value due to their clinical relevance in wide range of neuropsychiatric conditions spanning from anxiety to schizophrenia. Despite the massive therapeutic potential in modulating this system, the only clinically approved small molecule-based therapeutics (Mozavaptan, Conivaptan and Tolvaptan) are for use in the periphery. Cyclotide mimetics of the native neuropeptides are well explored in the literature although these scaffolds are unsuitable for application to the central nervous system. This work highlights non-peptidic natural products that are active within the neurohypophysial system that may be used to inspire future drug discovery endeavours.

Keywords: Arginine vasopressin; Drug discovery; Natural products; Neuropsychiatric disorders; Oxytocin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists* / pharmacology
  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Drug Discovery
  • Humans
  • Oxytocin / metabolism
  • Receptors, Oxytocin* / metabolism
  • Receptors, Vasopressin* / drug effects
  • Receptors, Vasopressin* / metabolism

Substances

  • Receptors, Vasopressin
  • Receptors, Oxytocin
  • Biological Products
  • Antidiuretic Hormone Receptor Antagonists
  • Oxytocin