Valnoctamide, valpromide and valnoctic acid are much less teratogenic in mice than valproic acid

Epilepsy Research
M RadatzH Nau

Abstract

The teratogenic properties of valproic acid (VPA) and its analogues depend to a great extent on their chemical structure. We investigated the structure-teratogenicity relationships of VPA, its structural isomer, valnoctic acid (VCA), and their two amide analogues, valpromide (VPD) and valnoctamide (VCD), respectively. Each substance was injected (3 mmol/kg) in NMRI-mice on the morning of day 8 of gestation. Embryolethality, fetal weight and exencephaly rates were recorded on day 18 of gestation. VPA caused 53% exencephaly, VPD induced 6%, VCA and VCD produced only 1% exencephaly (control values between 0 and 1%). VPA-treated mice also had increased embryolethality rates (52%). There was no significant change of embryolethality in the other treatment groups. Pharmacokinetic studies showed that VCD was eliminated from plasma at a slower rate than VPA. Also, the residual teratogenic activity of VPD was not accounted for by the relatively small amounts of its hydrolysis product VPA. This study indicates that VPD, VCA and VCD were distinctly less teratogenic than VPA. Apparently the amidation of the free carboxylic group and/or methyl-substitution at the beta-position of the carbon chain greatly decreased the teratogenic activity of...Continue Reading

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Citations

Mar 12, 2004·Epilepsy Research·Ofer SpiegelsteinRichard H Finnell
Dec 1, 2002·Clinical Neuroscience Research·Todd D GouldHusseini K Manji
Oct 16, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·M Bialer
Oct 29, 2013·Expert Opinion on Investigational Drugs·Lenka ČinčárováJiří Fajkus
Nov 27, 2009·Expert Opinion on Investigational Drugs·Pasquale Striano, Salvatore Striano
Dec 23, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gaetano Zaccara, Dieter Schmidt
Aug 21, 2015·Bipolar Disorders·Bogdan J WlodarczykRichard H Finnell
Jul 6, 2005·British Journal of Pharmacology·Ilan WinklerMeir Bialer
Jun 19, 2003·British Journal of Pharmacology·Nina IsoherranenMeir Bialer
May 31, 2006·Congenital Anomalies·Akinobu Okada, Michio Fujiwara
Apr 20, 2006·Epilepsy Research·Michael A Rogawski
May 16, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Lucio TremolizzoCarlo Ferrarese
Sep 23, 2016·Virology·Sara OrnaghiAnthony N van den Pol
Mar 3, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Akinobu OkadaMichio Fujiwara
Oct 17, 2018·Birth Defects Research·Ying Linda LinBogdan J Wlodarczyk
Mar 31, 2005·Birth Defects Research. Part A, Clinical and Molecular Teratology·Akinobu OkadaMichio Fujiwara
Oct 19, 2016·Clinical Neuropharmacology·Pasquale StrianoSalvatore Striano
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Nov 4, 2004·Birth Defects Research. Part A, Clinical and Molecular Teratology·Akinobu OkadaMichio Fujiwara

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