Histamine H3 receptor antagonists/inverse agonists: Where do they go?

  • Pharmacol Ther. 2019 Aug;200:69-84. doi: 10.1016/j.pharmthera.2019.04.007.
Nakisa Ghamari  1 ,  Omid Zarei  2 ,  José-Antonio Arias-Montaño  3 ,  David Reiner  4 ,  Siavoush Dastmalchi  1 ,  Holger Stark  5 ,  Maryam Hamzeh-Mivehroud  6
Affiliations
  • 1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 2. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran; Neurosciences Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
  • 3. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional 2508, Zacatenco, 07360 Ciudad de México, México.
  • 4. Heinrich Heine University Düsseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
  • 5. Heinrich Heine University Düsseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: [email protected].
  • 6. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
PMID: 31028835 DOI: 10.1016/j.pharmthera.2019.04.007
Abstract

Since the discovery of the histamine H3 receptor in 1983, tremendous advances in the pharmacological aspects of H3 receptor antagonists/inverse agonists have been accomplished in preclinical studies. At present, there are several drug candidates that reached clinical trial studies for various indications. However, entrance of these candidates to the pharmaceutical market is not free from challenges, and a variety of difficulties is engaged with their developmental process. In this review, the potential role of H3 receptors in the pathophysiology of various central nervous system, metabolic and allergic diseases is discussed. Thereafter, the current status for H3 receptor antagonists/inverse agonists in ongoing clinical trial studies is reviewed and obstacles in developing these agents are emphasized.

Keywords
Clinical trials; H(3) antagonists; H(3) inverse agonists; Histamine H(3) receptor; Neurological disorders; Pitolisant.
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