Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro

Slattery, Michael M.; Friel, Anne M.; Healy, David

doi:10.1016/s0029-7844(01)01522-8

Cited by 36 publications

(28 citation statements)

References 18 publications

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“…The magnitude of this inhibition is comparable to that of other established physiological and pharmacological uterorelaxant agents including human chorionic gonadotropin, cyclooxygenase inhibitors, b-adrenergic agonists, and oxytocin antagonists (Buscher et al 2001, Dennedy et al 2001, Slattery et al 2001, Doheny et al 2003. Abn-cbd has a potency of myometrial relaxation that is similar to the naturally occurring cannabinoids, anandamide (pD 2 value 5.58G0.42 and MMI value 75.8G2.20) and D 9 -tetrahydrocannabinol (pD 2 value 5.19G0.91 and MMI value 75.1G1.15; Dennedy et al 2004).…”

Section: Discussionmentioning

confidence: 57%

Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

Houlihan

Dennedy²

2010

Reproduction

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The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at elective cesarean section. The effects of cumulative doses of abn-cbd (10 K9 -10 K5 M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and doseresponse curves were constructed. The pD 2 (Klog EC 50 ) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractions in vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BK Ca channel antagonist, iberiotoxin, significantly attenuated this effect (for pD 2 , P!0.01; for MMI, P!0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BK Ca channel activity. These findings have implications for physiologic regulation of myometrial quiescence.

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Section: Discussionmentioning

confidence: 57%

Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

Houlihan

Dennedy²

2010

Reproduction

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“…Rofecoxib was dissolved in dimethyl sulfoxide (DMSO) which did not influence the contractile activity 21 . Atosiban was donated by Ferring Pharmaceutics Industries.…”

Section: Methodsmentioning

confidence: 99%

“…One study has been performed about in vitro uterine relaxant effect of celecoxib, a highly selective COX-2 inhibitor 21 . Celecoxib inhibits COX-2 activity 100 -400 times more than COX-1 and is more effective than preferential COX-2 inhibitors as tocolytic agents 18,19 .…”

Section: Concentrationsmentioning

confidence: 99%

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In vitro study of tocolytic effect of rofecoxib, a specific cyclo-oxygenase 2 inhibitor. Comparison and combination with other tocolytic agents

Doret¹

2002

BJOG: An International Journal of Obstetrics and Gynaecology

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Objective The aim of this work was to study and compare the tocolytic effects of rofecoxib with indomethacin, ritodrine, nicardipine and atosiban. We also studied the combination of rofecoxib with each agent. Design In vitro animal experimental study.Setting Non-selective cyclo-oxygenase (COX) inhibitors have potent tocolytic effect. However, they also have major fetal side effects that seem to be due to COX-1 inhibition. A specific COX-2 inhibitor could be a potent tocolytic agent with less fetal toxicity. Sample Myometrial strips from pregnant Wistar rats at 18 days of gestation.Methods Isometric tension was recorded from 112 pregnant rat myometrial strips in vitro. Strips were exposed to increase molar concentration of one drug or combination. Main outcome measures Contractile activity was assessed by calculating the area under the curve, to obtain a dose -response curve of each drug. EC 50 and mean maximal inhibiting concentration were compared using ANOVA. Chemical interaction was defined for each combination. Results The in vitro tocolytic effect of rofecoxib was demonstrated. Contractile activity stopped at a concentration of 1.6Â10 À7 M. Effective concentrations were 1000 times less than for indomethacin and significantly lower than ritodrine and atosiban. Rofecoxib combined with ritodrine had a synergic effect. Other combinations only had an additive effect. Conclusions Rofecoxib has a potent tocolytic effect in vitro. The high specificity and low effective concentrations of COX-2 may result in low fetal toxicity. Animal fetal side effects need to be explored.

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“…The effects of these enzymes include inhibition of ovulation, prevention of implantation as well as adhesion after surgery and the inhibition of premature labour (Muzii et al 1998;Salhab et al 2001;Slattery et al 2001;Shafiq et al 2004;Botting 2006;Gaytan et al 2006). Numerous studies have been carried out to determine the importance of the COX enzyme in implantation.…”

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confidence: 99%

Evaluation of the contraceptive effects of carprofen, flunixin meglumine and meloxicam in rats

Paksoy¹,

Kirbaş²

2017

Vet. Med. - Czech

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ABSTRACT:The objective of this study was to determine the suitability of carprofen, flunixin meglumine and meloxicam for use in emergency contraception. Forty-eight pregnant Sprague-Dawley rats were used as material. Five groups were subjected to treatments while one group served as a control. The numbers of animals in each group were equal (n = 8). Treatment groups were administered carprofen (10 mg/kg, single or double dose, s.c.), flunixin meglumine (5 mg/kg, single or double dose, i.m.) and meloxicam (2 mg/kg, a single dose, s.c.) on the third day after mating. The control group received saline. The rats were sacrificed on Day 7 of gestation. Luteal spots and implantation sites were recorded. Pre-implantation loss was calculated by subtracting the number of luteal spots from the number of implantation sites. Compared with the control, the administration of flunixin meglumine (double dose), carprofen (double dose) and meloxicam highly significantly decreased the implantation rate (P < 0.001). Single dose administration of flunixin meglumine and carprofen led to significant decreases (P < 0.01). In conclusion, this study indicates that carprofen, flunixin meglumine and meloxicam treatment cause a decline in implantation rate in rats.

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Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro

Abstract: COX-2 inhibitors exert significant relaxation in human myometrium with a similar potency in nonpregnant and pregnant (before and after labor onset) tissues. Celecoxib, a COX-2 specific inhibitor, was more potent than nimesulide or meloxicam, COX-2 preferential inhibitors.

Cited by 36 publications

References 18 publications

Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

In vitro study of tocolytic effect of rofecoxib, a specific cyclo-oxygenase 2 inhibitor. Comparison and combination with other tocolytic agents

Evaluation of the contraceptive effects of carprofen, flunixin meglumine and meloxicam in rats

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