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Assessing the Potency of the Novel Tocolytics 2-APB, Glycyl-H-1152, and HC-067047 in Pregnant Human Myometrium.
- Source :
-
Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2023 Jan; Vol. 30 (1), pp. 203-220. Date of Electronic Publication: 2022 Jun 17. - Publication Year :
- 2023
-
Abstract
- The intracellular signaling pathways that regulate myometrial contractions can be targeted by drugs for tocolysis. The agents, 2-APB, glycyl-H-1152, and HC-067047, have been identified as inhibitors of uterine contractility and may have tocolytic potential. However, the contraction-blocking potency of these novel tocolytics was yet to be comprehensively assessed and compared to agents that have seen greater scrutiny, such as the phosphodiesterase inhibitors, aminophylline and rolipram, or the clinically used tocolytics, nifedipine and indomethacin. We determined the IC <subscript>50</subscript> concentrations (inhibit 50% of baseline contractility) for 2-APB, glycyl-H-1152, HC-067047, aminophylline, rolipram, nifedipine, and indomethacin against spontaneous ex vivo contractions in pregnant human myometrium, and then compared their tocolytic potency. Myometrial strips obtained from term, not-in-labor women, were treated with cumulative concentrations of the contraction-blocking agents. Comprehensive dose-response curves were generated. The IC <subscript>50</subscript> concentrations were 53 µM for 2-APB, 18.2 µM for glycyl-H-1152, 48 µM for HC-067047, 318.5 µM for aminophylline, 4.3 µM for rolipram, 10 nM for nifedipine, and 59.5 µM for indomethacin. A single treatment with each drug at the determined IC <subscript>50</subscript> concentration was confirmed to reduce contraction performance (AUC) by approximately 50%. Of the three novel tocolytics examined, glycyl-H-1152 was the most potent inhibitor. However, of all the drugs examined, the overall order of contraction-blocking potency in decreasing order was nifedipine > rolipram > glycyl-H-1152 > HC-067047 > 2-APB > indomethacin > aminophylline. These data provide greater insight into the contraction-blocking properties of some novel tocolytics, with glycyl-H-1152, in particular, emerging as a potential novel tocolytic for preventing preterm birth.<br /> (© 2022. The Author(s).)
- Subjects :
- Infant, Newborn
Pregnancy
Humans
Female
Nifedipine pharmacology
Nifedipine metabolism
Myometrium metabolism
Rolipram metabolism
Rolipram pharmacology
Aminophylline metabolism
Aminophylline pharmacology
Uterine Contraction
Indomethacin metabolism
Indomethacin pharmacology
Tocolytic Agents pharmacology
Premature Birth metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1933-7205
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Reproductive sciences (Thousand Oaks, Calif.)
- Publication Type :
- Academic Journal
- Accession number :
- 35715551
- Full Text :
- https://doi.org/10.1007/s43032-022-01000-2