Synergism between β2-adrenoceptor agonists and subtype-selective α1A-adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro

A. Mihályi, R. Gáspár, D. Csonka, G. Falkay

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

1. Despite great efforts in recent decades, premature birth is still a leading cause of perinatal morbidity and mortality. β2-Adrenoceptor agonists are frequently used as tocolytics, although their use is rather controversial. Previous animal studies have revealed that blockade of α1A-adrenoceptors results in relaxation of the pregnant rat myometrium. 2. The aim of the present study was to investigate the uterus relaxant effect of the β2-adrenoceptor agonists (terbutaline, ritodrin) applied together with the subtype-selective α1A-adrenoceptor antagonists (WB 4101, 5-methyl-urapidil) in an in vitro rat model. The main objective of the experiments was to clarify whether there was an additive or a potentiating synergism between the two drug classes. 3. Myometrial rings were taken from female, 22-day pregnant (end-term) Sprague-Dawley rats. Electrical field stimulation (EFS) was used to elicit rhythmical contractions. Non-cumulative concentration-response curves were constructed to the β2-adrenoceptor agonists and the α1A-adrenoceptor antagonists alone and to β2-adrenoceptor agonists co-administered with the α1A-adrenoceptor antagonists. 4. Both groups of drugs inhibited EFS-induced contractions in a dose-dependent way. Administering the β2-adrenoceptor agonists in combination with the α1A-adrenoceptor antagonists resulted in a significant decrease in the EC50 and an increase in the maximal contraction inhibiting effect. 5. The potentiating synergism that has been revealed between β2-adrenoceptor agonists and α1A-adrenoceptor antagonists in the uterus relaxant effect may be of great clinical importance because it could improve the efficacy of therapy of preterm delivery.

Original languageEnglish
Pages (from-to)164-167
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

Fingerprint

Tocolytic Agents
Adrenergic Receptors
Uterus
Electric Stimulation
In Vitro Techniques
Terbutaline
Myometrium
Perinatal Mortality
Premature Birth
Pharmaceutical Preparations
Sprague Dawley Rats

Keywords

  • α-adrenoceptor antagonists
  • β-adrenoceptor agonists
  • Combination
  • Electric field stimulation
  • Rat
  • Tocolysis

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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title = "Synergism between β2-adrenoceptor agonists and subtype-selective α1A-adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro",
abstract = "1. Despite great efforts in recent decades, premature birth is still a leading cause of perinatal morbidity and mortality. β2-Adrenoceptor agonists are frequently used as tocolytics, although their use is rather controversial. Previous animal studies have revealed that blockade of α1A-adrenoceptors results in relaxation of the pregnant rat myometrium. 2. The aim of the present study was to investigate the uterus relaxant effect of the β2-adrenoceptor agonists (terbutaline, ritodrin) applied together with the subtype-selective α1A-adrenoceptor antagonists (WB 4101, 5-methyl-urapidil) in an in vitro rat model. The main objective of the experiments was to clarify whether there was an additive or a potentiating synergism between the two drug classes. 3. Myometrial rings were taken from female, 22-day pregnant (end-term) Sprague-Dawley rats. Electrical field stimulation (EFS) was used to elicit rhythmical contractions. Non-cumulative concentration-response curves were constructed to the β2-adrenoceptor agonists and the α1A-adrenoceptor antagonists alone and to β2-adrenoceptor agonists co-administered with the α1A-adrenoceptor antagonists. 4. Both groups of drugs inhibited EFS-induced contractions in a dose-dependent way. Administering the β2-adrenoceptor agonists in combination with the α1A-adrenoceptor antagonists resulted in a significant decrease in the EC50 and an increase in the maximal contraction inhibiting effect. 5. The potentiating synergism that has been revealed between β2-adrenoceptor agonists and α1A-adrenoceptor antagonists in the uterus relaxant effect may be of great clinical importance because it could improve the efficacy of therapy of preterm delivery.",
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T1 - Synergism between β2-adrenoceptor agonists and subtype-selective α1A-adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro

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AU - Gáspár, R.

AU - Csonka, D.

AU - Falkay, G.

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