Valpromide inhibits human epoxide hydrolase.

Pacifici, Gian Maria; Franchi, M; Bencini, Chiara; Rane, Anders

doi:10.1111/j.1365-2125.1986.tb02886.x

Cited by 21 publications

(11 citation statements)

References 23 publications

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“…Since the latter is cleared virtually entirely by conversion to the corresponding diol by epoxide hydrolase (Tomson et al, 1983;Bertilsson & Tomson, 1986), our data can be regarded as strong for evidence for the occurrence of in vivo inhibition of this enzyme. Such a mechanism of interaction is further supported by increased plasma levels of CBZ-E during combined therapy with CBZ and VPM (Meijer etal., 1985;Pisani et al, 1986) and by in vitro experiments showing that VPM is a powerful inhibitor of epoxide hydrolase in monkey (Pacifici et al, 1985) and human (Pacifici et al, 1986) liver microsomes.…”

Section: Discussionmentioning

confidence: 99%

Effect of valpromide on the pharmacokinetics of carbamazepine‐10, 11‐ epoxide.

Pisani

Fazio

Oteri

et al. 1988

Brit J Clinical Pharma

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The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 ± 1.4 to 20.5 ± 6.3 h and decreased CBZ-E clearance from 73.5 ± 20.0 to 23.5 ± 4.0 ml h-' kg-' (P < 0.01). These results suggest that the elevation of plasma CBZ-E levels in patients receiving carbamazepine and VPM in combination is due to inhibition of epoxide hydrolase in the liver.

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Section: Discussionmentioning

confidence: 99%

Effect of valpromide on the pharmacokinetics of carbamazepine‐10, 11‐ epoxide.

Pisani

Fazio

Oteri

et al. 1988

Brit J Clinical Pharma

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“…The administration of valpromide and epileptic drugs, such as carbamazepine, increases the plasma concentration of the metabolite carbamazepine‐10,11‐epoxide. Such effect on carbamazepine epoxide elimination results from an inhibition of epoxide hydrolase activity …”

Section: Resultsmentioning

confidence: 99%

Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations

Saenz‐Méndez

Katz²,

Pérez-Kempner³

et al. 2017

Proteins

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A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble-based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720-730. © 2016 Wiley Periodicals, Inc.

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“…This anti-epileptic drug has been shown to competitively inhibit a number of structurally different EHs. 5,7 Figure 1. Ligands and enzymatic mechanism of Rv2740 and LEH.…”

Section: Specificitymentioning

confidence: 98%