Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine

Lipids. 1991 Dec;26(12):1172-4. doi: 10.1007/BF02536525.

Abstract

From a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet-activating factor (PAF) and histamine antagonist, Sch 37370, namely 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo- [5,6]cyclohepta[1,2-b]pyridin-11-ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF-induced aggregation of human platelets in vitro (IC50 = 0.6 microM), and in vivo inhibits PAF- and histamine-induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.

Publication types

  • Comparative Study

MeSH terms

  • Histamine Antagonists / pharmacology*
  • Humans
  • Kinetics
  • Loratadine / analogs & derivatives
  • Male
  • Piperidines / chemical synthesis
  • Piperidines / pharmacology*
  • Platelet Activating Factor / antagonists & inhibitors*
  • Platelet Activating Factor / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Histamine Antagonists
  • Piperidines
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Loratadine
  • N-acetyldesloratadine