{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:34:41Z","timestamp":1776850481129,"version":"3.51.2"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Pharmacol Ther"],"abstract":"<jats:p>The antiepileptic drug valproic acid (VPA) has been implicated as a\nhuman teratogen causing spina bifida aperta. Recently we developed a\nmouse model inducing spina bifida aperta and occulta with VPA. In a\nsearch for novel antiepileptic agents the VPA metabolite E-2-n-propyl-2-\npentenoic acid (2-en-VPA) had been developed. In the mouse, 2-en-VPA\nexhibits anticonvulsive potency similar to VPA but very low teratogenic\npotency (induction of exencephaly). We have now compared VPA and its\nmetabolite 2-en-VPA in regard to induction of spina bifida in our mouse\nmodel. 2-en-VPA was administered 3 times during the period of gestation\nmost sensitive for the induction of spina bifida aperta with VPA: on day 9\nof gestation at 0, 6 and 12 h. The following doses were injected (in mmol\n2-en-VPA-Na\/kg): (a) 3 x 2.1, (b) 3 x 2.7 (the equimolar dose of VPA is\nthe threshold dose for induction of spina bifida aperta) and (c) 3 x 3.0 (the\nequimolar VPA dose produced spina bifida aperta). 2-en-VPA did not\ninduce spina bifida aperta in the mouse in any of these groups. We then\ninvestigated the induction of spina bifida occulta in the three dose groups.\nSpina bifida occulta is a less serious form of spina bifida and may provide\na sensitive method to estimate the potency of a compound to induce more\nsevere forms of spina bifida. This malformation was demonstrated in\nalcian-blue- and alizarin-red-stained fetal skeletons by measurements of\nthe distance between the cartilaginous ends of each vertebral arch. Spina\nbifida occulta was not induced by 2-en-VPA; equimolar doses of VPA\ninduced spina bifida occulta to a high percentage. Our results indicate that\nthe multiple and high doses of 2-en-VPA on day 9 of gestation did not\ninduce spina bifida aperta or spina bifida occulta in the mouse. The low\nteratogenic potency of 2-en-VPA in comparison with VPA was thus demonstrated\nwith the hallmark defect induced by antiepileptic therapy with\nVPA in the human.<\/jats:p>","DOI":"10.1159\/000457485","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T17:08:25Z","timestamp":1502471305000},"page":"196-204","source":"Crossref","is-referenced-by-count":6,"title":["The Valproic Acid Metabolite E-2-n-Propyl-2-Pentenoic Acid Does Not Induce Spina bifida in the Mouse"],"prefix":"10.1159","author":[{"given":"Katharine","family":"Ehlers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"St\u00fcrje","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Joachim","family":"Merker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinz","family":"Nau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,8,11]]},"container-title":["Developmental Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000457485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:34:28Z","timestamp":1776846868000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000457485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000457485","archive":["Portico"],"relation":{},"ISSN":["0379-8305","2504-2505"],"issn-type":[{"value":"0379-8305","type":"print"},{"value":"2504-2505","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]}}}