{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T03:21:06Z","timestamp":1778556066893,"version":"3.51.4"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"REDES-PRODEP-SEP","award":["Red Tem\u00e1tica: Farmacolog\u00eda de la Reproducci\u00f3n"],"award-info":[{"award-number":["Red Tem\u00e1tica: Farmacolog\u00eda de la Reproducci\u00f3n"]}]},{"name":"FOSISS-CONACyT","award":["Salud-2010-C01-139715"],"award-info":[{"award-number":["Salud-2010-C01-139715"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K+-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 \u00b1 13.72 and 98.45 \u00b1 8.86 \u00b5M, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p &lt; 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.<\/jats:p>","DOI":"10.3390\/molecules21101332","type":"journal-article","created":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T10:35:19Z","timestamp":1476095719000},"page":"1332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3280-1323","authenticated-orcid":false,"given":"Eduardo","family":"Fern\u00e1ndez-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Biolog\u00eda de la Reproducci\u00f3n, \u00c1rea Acad\u00e9mica de Medicina del Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca 42090, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Ponce-Monter","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Biolog\u00eda de la Reproducci\u00f3n, \u00c1rea Acad\u00e9mica de Medicina del Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca 42090, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Soria-Jasso","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Biolog\u00eda de la Reproducci\u00f3n, \u00c1rea Acad\u00e9mica de Medicina del Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca 42090, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Biolog\u00eda de la Reproducci\u00f3n, \u00c1rea Acad\u00e9mica de Medicina del Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca 42090, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9-Antonio","family":"Arias-Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del IPN, Apdo. Postal 14-740, M\u00e9xico City 07360, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Barrag\u00e1n-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Hospital General de los SSH, Pachuca 42070, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"May\u00e9n-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Biolog\u00eda de la Reproducci\u00f3n, \u00c1rea Acad\u00e9mica de Medicina del Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Pachuca 42090, Hidalgo, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2393-7-S1-S2","article-title":"Overview. 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