title: Anxiolytic and antidepressant-like activities of the novel and potent non-imidazole histamine H₃ receptor antagonist ST-1283.
abstract: Previous studies have suggested a potential link between histamine H₃ receptors (H₃R) signaling and anxiolytic-like and antidepressant-like effects. The aim of this study was to investigate the acute effects of ST-1283, a novel H₃R antagonist, on anxiety-related and depression-related behaviors in comparison with those of diazepam and fluoxetine. The effects of ST-1283 were evaluated using the elevated plus maze test, open field test, marbles burying test, tail suspension test, novelty suppressed feeding test, and forced swim test in male C57BL/6 mice. The results showed that, like diazepam, ST-1283 (7.5 mg/kg) significantly modified all the parameters observed in the elevated plus maze test. In addition, ST-1283 significantly increased the amount of time spent in the center of the arena without altering general motor activity in the open field test. In the same vein, ST-1283 reduced the number of buried marbles as well as time spent digging in the marbles burying test. The tail suspension test and forced swim test showed that ST-1283 was able to reduce immobility time, like the recognized antidepressant drug fluoxetine. In the novelty suppressed feeding test, treatment with ST-1283 decreased latency to feed with no effect on food intake in the home cage. Importantly, pretreatment with the H₃R agonist R-α-methylhistamine abrogated the anxiolytic and antidepressant effects of ST-1283. Taken together, the present series of studies demonstrates the novel effects of this newly synthesized H₃R antagonist in a number of preclinical models of psychiatric disorders and highlights the histaminergic system as a potential therapeutic target for the treatment of anxiety-related and depression-related disorders.
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Amine
authors.initials: A
authors.lastname: Bahi
authors.affiliation: Institut für Pharmazeutische Chemie, Biozentrum, Johann Wolfgang Goethe University, Frankfurt, Germany ; Heinrich Heine University Duesseldorf, Institut fuer Pharmazeutische and Medizinische Chemie, Düsseldorf, Germany.
authors.forename: Johannes Stephan
authors.initials: JS
authors.lastname: Schwed
authors.affiliation: Institut für Pharmazeutische Chemie, Biozentrum, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Walter
authors.affiliation: Heinrich Heine University Duesseldorf, Institut fuer Pharmazeutische and Medizinische Chemie, Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D054828:Histamine H3 Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000597392:3-(5-methyl-4-(4-(3-(piperidin-1-yl)propoxy)phenyl)-4H-1,2,4-triazol-3-yl)pyridine; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D054828:Histamine H3 Antagonists; D011725:Pyridines; D018100:Receptors, Histamine H3; D014230:Triazoles
keywords: H3 receptor; R-α-methylhistamine; ST-1283; anxiety; depression; histamine