Medicinal chemistry of 5-HT5A receptor ligands: A receptor subtype with unique therapeutical potential

Balázs Volk, Bence J. Nagy, Szilvia Vas, Diána Kostyalik, Gyula Simig, György Bagdy

Research output: Contribution to journalArticle

24 Citations (Scopus)


Although the 5-HT5 receptor subfamily was discovered more than 15 years ago, it is unambiguously the least known 5-HT receptor subtype. The Gi/Go-mediated signal transduction and its intensive presence in raphe and other brainstem and pons nuclei suggest mechanisms similar to those of 5-HT1 receptors, the ligands of which are already applied in the treatment of e.g. anxiety and migraine. In addition, a unique coupling and inhibition of adenosine diphosphate-ribosyl cyclase have also been described. High concentrations of 5-HT5 receptor in other key regions including, e.g. locus coeruleus, nucleus of the solitary tract, arcuate and suprachiasmatic nuclei of the hypothalamus indicate a wide range of physiological effects, thus its ligands are potential drug candidates in various areas, e.g. anxiety, sleep, incontinence, food intake, learning and memory, pain or chemoreception pathways. These findings have motivated several institutes and pharmaceutical companies to participate in the research of this field, Despite extensive research, no selective agonist and only two selective antagonists have been identified until now. Beyond these compounds, the present review provides a complete overview on all other published 5-HT5A receptor ligands as well as on the structure, function, distribution, genetics and possible therapeutic applications of this receptor.

Original languageEnglish
Pages (from-to)554-578
Number of pages25
JournalCurrent topics in medicinal chemistry
Issue number5
Publication statusPublished - Apr 1 2010


  • 5-HT autoreceptor
  • 5-HT, 5-HT
  • Anxiety
  • Drug target
  • Food intake
  • Incontinence
  • Learning and memory
  • Neuronal hyperpolarization
  • Pain
  • Serotonin
  • Sleep

ASJC Scopus subject areas

  • Drug Discovery

Fingerprint Dive into the research topics of 'Medicinal chemistry of 5-HT<sub>5A</sub> receptor ligands: A receptor subtype with unique therapeutical potential'. Together they form a unique fingerprint.

  • Cite this