N-substituted 11-(4-piperidylene)-5,6-dihydro-11H-benzo-[5,6]cyclohepta [1,2-b]pyridines. Antihistamines with no sedating liability

Arzneimittelforschung. 1986 Sep;36(9):1311-4.

Abstract

Conversion of the basic tertiary amino function of the potent antihistamine, azatadine (Optimine), to neutral carbamate function results in compounds which retain significant antihistamine activity with little or no CNS effects. In guinea pigs the N-ethoxycarbonyl derivative 4 had the same antihistamine potency as terfenadine, a clinically used non-sedating antihistamine. In mice, 4 was a potent antihistamine while lacking CNS effects. The 8-chloro-N-ethoxycarbonyl 5 (loratadine, Sch 29851) was the most potent antihistamine in the series, had no CNS side effects, and was selected for clinical evaluation.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / chemical synthesis
  • Cyproheptadine / pharmacology
  • Cyproheptadine / toxicity
  • Female
  • Guinea Pigs
  • Histamine Antagonists / adverse effects
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / pharmacology
  • Hypnotics and Sedatives
  • Loratadine
  • Male
  • Mice

Substances

  • Histamine Antagonists
  • Hypnotics and Sedatives
  • Cyproheptadine
  • Loratadine