Beta-3 versus beta-2 adrenergic agonists and preterm labour: in vitro uterine relaxation effects

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Abstract
1. To investigate the effects of the selective beta-3 adrenoreceptor agonist, BRL 37344, on human pregnant myometrial contractility in vitro. 2. to compare these effects with those of the beta-2 adrenoreceptor agonist, ritodrine. Isometric tension recording was performed under physiological conditions in isolated myometrial strips from biopsies obtained at elective caesarean section. Following pre-incubation with oxytocin (10(-9) M), the effects of cumulative additions of BRL 37344 or ritodrine (10(-8)-10(-3.5) M) on myometrial contractility were investigated. Results were expressed as -log EC50 (pD2) and mean maximal inhibition achieved for both drug compounds. BRL 37344 exerted a concentration dependant relaxant effect on myometrial contractions in all strips exposed [pD2, 7.26 (0.48) (SEM); mean maximal inhibition 61.98 (4.89%); n = 6]. Similarly, ritodrine exerted a concentration dependant inhibition of myometrial contractility in all strips exposed [pD2 = 7.40 (0.28); mean maximal inhibition 59.49 (3.97%); n = 6]. There was no significant difference between calculated pD2 values (P = 0.65) or mean maximal inhibition achieved (P = 0.79). The beta-3 adrenoreceptor agonist BRL 37344 induced relaxation of human myometrial contractions with similar potency to that of the most commonly used tocolytic agent ritodrine. This raises the possibility that the novel beta-3 adrenoreceptor agonists may have potential as therapeutic agents for human preterm labour. In view of their reported reduced cardiovascular side effects their potential clinical use requires further evaluation.

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