Valpromide derivatives

Apart from valpromide derivatives, there are only few other drugs with a primary amide group that undergo metabolic hydrolysis. One example is that of metopimazine (4.23), a phenothiazine with antiemetic properties. Its carboxylic acid 4.24 was the major urinary metabolite in rabbits, but was not formed in dogs [8],... 

Tasso SM, Moon S, Bruno-Blanch LE, Estiu GL. Characterization of the anticonvulsant profile of valpromide derivatives. Bioorg Med Chem 2004 12 3857-69. 

The latter stages of carbamazepine metabolism appear to be inhibited by both valproate and its amide derivative, valpromide. The levels of the metabolite earbamazepine-,10,11-epoxide increase during concurrent use, probably by inhibition of its metabolism to carbamazepine-10,11-trans-di-qI 28-30 jy epoxide hydrolase. Valpromide was found to be about 100 times more potent an inhibitor of this enzyme than sodium valproate in wtro and caused a threefold higher rise in epoxide levels than valproate in one study. The carbamazepine-10,11-epoxide metabolite has antieonvulsant activity, but it may also cause toxicity if its serum levels beeome exees-sive. ... 

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