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Synergism between β 2 ‐adrenoceptor agonists and subtype‐selective α 1A ‐adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro
Author(s) -
Mihályi A,
Gáspár R,
Csonka D,
Falkay G
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03811.x
Subject(s) - myometrium , tocolytic agent , terbutaline , medicine , stimulation , pharmacology , agonist , endocrinology , tocolytic , intrinsic activity , uterus , adrenergic receptor , receptor , pregnancy , preterm labor , fetus , biology , asthma , genetics
Summary 1. Despite great efforts in recent decades, premature birth is still a leading cause of perinatal morbidity and mortality. β 2 ‐Adrenoceptor agonists are frequently used as tocolytics, although their use is rather controversial. Previous animal studies have revealed that blockade of α 1A ‐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 β 2 ‐adrenoceptor agonists (terbutaline, ritodrin) applied together with the subtype‐selective α 1A ‐adrenoceptor antagonists (WB 4101, 5‐methylurapidil) 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 β 2 ‐adrenoceptor agonists and the α 1A ‐adrenoceptor antagonists alone and to β 2 ‐adrenoceptor agonists co‐administered with the α 1A ‐adrenoceptor antagonists. 4. Both groups of drugs inhibited EFS‐induced contractions in a dose‐dependent way. Administering the β 2 ‐adrenoceptor agonists in combination with the α 1A ‐adrenoceptor antagonists resulted in a significant decrease in the EC 50 and an increase in the maximal contraction inhibiting effect. 5. The potentiating synergism that has been revealed between β 2 ‐adrenoceptor agonists and α 1A ‐adrenoceptor antagonists in the uterus relaxant effect may be of great clinical importance because it could improve the efficacy of therapy of preterm delivery.