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A Molecular Container for Ergometrine
Abstract Number: T-10
Abstract Type: Original Research
Introduction: Hypertensive disorders and postpartum hemorrhage account for 25% of maternal mortality . Oxytocin(MW=1000) given as an intravenous bolus can cause hypotension and ST segment depression. Methergine(MW=339) can cause hypertension , coronary and cerebral vasospasm. Drug encapsulation by molecular containers is used to attenuate the toxicity of cisplatin used for ovarian chemotherapy. Would methergine bind to a macrocycle enabling more drug to reach uterine receptors, sparing other targets?
Methods: A series of isothermal calorimetric titrations was conducted to determine the affinity of macrocycles( calixarenes and cucurbiturils) to methergine.
Results: Cucurbituril binds methergine with a ka = 1.4x10^4/M.(figure)
Discussion: Sugammadex reverses a rocuronium neuromuscular block by binding with a Ka = 10^7/M . Cucurbituril binds diplatin with a ka = 10^5/M. There are over one million organophosphate poisonings per year treated with atropine which is difficult to titrate-to–effect. This leads to an anticholinergic toxidrome. However, atropine overdose is amenable to chelation with cucurbituril. It may be possible to use higher doses of ergot alkaloids to treat postpartum hemorrhage and then to encapsulate excess drug.
References: Berg,Obstet Gynec( 2010)116:1302-09 Wheate,J. Inorg.Chem (2008)102:2060-2066