Histamine receptors


Histamine receptors are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [1]. The human and rat H3 receptor genes are subject to significant splice variance [2]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [3]. Some agonists at the human H3 receptor display significant ligand bias [4]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [3] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [5,6].


  1. Hill SJ, Ganellin CR, Timmerman H, et al. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 1997;49:253-78.
  2. Bakker RA, Lozada AF, van Marle A, et al. Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant-negative isoforms. Mol Pharmacol 2006;69:1194-206.
  3. Panula P, Chazot PL, Cowart M, et al. International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors. Pharmacol Rev 2015;67:601-55.
  4. Riddy DM, Cook AE, Diepenhorst NA, et al. Isoform-Specific Biased Agonism of Histamine H3 Receptor Agonists. Mol Pharmacol 2017;91:87-99.
  5. Venail F, Attali P, Wersinger E, et al. Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H4 receptor inhibitor SENS-111 using a modified caloric test in healthy subjects. Br J Clin Pharmacol 2018;84:2836-2848.
  6. Attali P, Gomeni R, Wersinger E, et al. The Effects of SENS-111, A New H4R Antagonist, On Vertigo Induced by Caloric Test in Healthy Volunteers (HV) is Related to Plasma Concentrations. Clin Ther 2016;38:e4.
Excerpt from IUPHAR/BPS Guide to Pharmacology
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