Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.1.4 (
deaminase
)
5,113
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In mice, the diethylglycineamide analogue of
LY201116
, DEGA (N-(2,6-dimethylphenyl)-4-[[(diethylamino)acetyl]amino]benzamide), is metabolized by consecutive N-deethylations for form MEGA and GA; the monoethylglycineamide and glycineamide analogues of
LY201116
, respectively. All of these compounds are in turn hydrolyzed to form
LY201116
[4-amino-N-(2,6-dimethylphenyl)benzamide].
LY201116
is N-acetylated to form the N-acetyl metabolite, NAC. NAC is also deacetylated to reform
LY201116
. All of the above compounds inhibit maximal electroshock-induced seizures (MES) in mice. After oral administration, the potencies of these compounds were similar at their time of peak anticonvulsant effect. However, the MES ED50 values for the above compounds 5 min after iv dosing were 43, 13, 2, and 0.5 mg/kg for DEGA, MEGA, GA, and
LY201116
, respectively. Similar plasma levels of
LY201116
were produced in mice 5 min after iv dosing with the respective ED50 values of the above compounds, which suggested that all of the compounds produced their anticonvulsant effects via
LY201116
. The in vivo metabolism of DEGA and MEGA but not GA to
LY201116
was inhibited by the
acylamidase
inhibitor bis-(p-nitrophenyl) phosphate (BNPP). Mice predosed with BNPP were not protected by DEGA and MEGA from MES-induced seizures and the plasma samples contained little or no
LY201116
. The metabolism of GA to
LY201116
was not inhibited by BNPP, and GA was an active anticonvulsant in BNPP-pretreated mice. The apparent iv potency of DEGA increased dramatically with time after dosing, again suggesting time-dependent, metabolically mediated liberation of the more potent anticonvulsant
LY201116
.
...
PMID:Metabolism of the prodrug DEGA (N-(2,6-dimethylphenyl)-4-[[(diethylamino)acetyl]amino]benzamide) to the potent anticonvulsant LY201116 in mice. Effect of bis-(p-nitrophenyl)phosphate. 290 94
