High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

• Publication year

  1998

• Venue

  European Journal of Pharmacology

• Publication date

  1998-06-26

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/S0014-2999(98)00396-3PMID 9721022
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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