Preterm labour: an overview of current and emerging therapeutics.
Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the US FDA and still remains the standard therapy for treating preterm labour. Ritodrine (Yutopar( trade mark )) stimulates the beta(2)-adrenergic receptor throughout the body, causing an inhibitory action in different tissues that, among other side effects, also leads to an attenuation of uterine contractility. More recently, a new therapeutic agent, atosiban (Tractocile( trade mark )), a peptidic oxytocin receptor antagonist, has been introduced to the market. However, the use of the various pharmacological agents to treat preterm labour remains restricted, due to lack of uterine selectivity, low efficacy and potentially serious side effects for the mother or the foetus. Therefore, there is an urgent need to develop drugs with myometrial selectivity that would allow long-lasting inhibition of labour and prolong pregnancy up to a stage when good foetal maturation raises the chances of survival. One of the major obstacles hampering the development of new therapeutic agents is the marked inter-species difference in terms of preterm labour physiology, which complicates the preclinical evaluation of new candidate molecules in animal models of disease. In this review, the authors will provide a comprehensive update of past, current and new approaches for the management of preterm labour, including beta(2)-adrenergic agonists, calcium channel blockers, oxytocin antagonists, prostaglandin antagonists and other potential therapeutics. For each of the therapies used today, the review will cover the mechanism of action, benefit and adverse effects, and discuss the promise and potential benefits of new emerging therapeutic agents.
Schwarz
Matthias K
MK
Department of Medicinal Chemistry - Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland.
Page
Patrick
P
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D008278:Magnesium Sulfate / Q000009:adverse effects / Q000494:pharmacology; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000517:prevention & control; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000502:physiology; D011247:Pregnancy; D011448:Prostaglandin Antagonists / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D010121:Oxytocin; D008278:Magnesium Sulfate