Alpha-adrenergic blockade: a possible mechanism of tocolytic action of certain benzodiazepines in a postpartum rat model in vivo

Life Sci. 2003 Jan 24;72(10):1093-102. doi: 10.1016/s0024-3205(02)02306-8.

Abstract

Benzodiazepines are frequently used for the treatment of maternal psychiatric disorders during pregnancy. Besides their anxiolytic effect, they are reported to exert a direct relaxing action on several smooth muscle preparations, including the uterus. In the present study, the possibility of the involvement of alpha(1)-adrenergic receptors in this peripheral effect is investigated. The tocolytic potencies of diazepam, midazolam and nitrazepam are assessed in vivo in a postpartum rat model, together with other drugs known to bind to alpha-adrenoceptors (e.g. alpha(1)-antagonists, tricyclic compounds and droperidol). The interactions of some benzodiazepines and norepinephrine were also examined in an isolated in vitro system. The affinities of these agents for the receptor in question were additionally tested by radioligand displacement assay. A correlation was found between the tocolytic potencies and inhibition constants of the tested drugs, suggesting that the smooth muscle-relaxing effect of these benzodiazepines is mediated through modulation of the alpha(1)-adrenergic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Benzodiazepines / pharmacology*
  • Diazepam / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • In Vitro Techniques
  • Myometrium / drug effects
  • Myometrium / metabolism
  • Nitrazepam / pharmacology
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology
  • Postpartum Period
  • Pregnancy
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Tocolytic Agents / pharmacology*
  • Uterine Contraction / drug effects

Substances

  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-1
  • Tocolytic Agents
  • Benzodiazepines
  • Nitrazepam
  • Diazepam
  • Norepinephrine