[The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076)].

Paper

[The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076)].

Published Nov 1, 1993 · A. Langner, J. Rätzer, H. Rickert

Die Pharmazie

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1

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Abstract

4-p-Chlorphenylpyrrole-3-morpholino-2-carboxylic acid methylester (1; AWD 140-076) is a substance with anticonvulsive properties. After p.o. administration in male wistar rats many metabolites in relatively small concentration are excreted in urine and faeces, six of them could be isolated and identified as quantitative dominating compounds. Compound 1 is attacked in different sites of the molecule by the cytochrome P-450 system. At the morphine ring N- and O-dealkylation reactions take place leading to the cleavage of the ring. After that a stepwise degradation by oxidative and reductive processes occurs. Further reactions concern the N-oxidation of the morpholine nitrogen as well as the hydroxylation of the pyrrole skeleton forming the main metabolites. 5 metabolites are also present as sulfate or glucuronide conjugates. The quantity ratio of the phase I to phase II metabolites amounts to 9:1. In the in vitro test system isolated perfused rat liver and rat hepatocytes culture solely the two main metabolites are formed. Compound 1 is characterized by enzyme inducing activities. The oxidative demethylation of p-nitroanisole is increased 4-fold after pretreatment.

In Vitro Study

Study Snapshot

The anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076) undergoes complex biotransformation, forming six dominating compounds in urine and feces, with a 9:1 ratio of

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

[The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076)].

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References

Citations

Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026

NU7026, a novel DNA-PK inhibitor, shows potential for radiosensitization in ovarian cancer, but requires four daily doses of 100 mg kg1 i.p. to achieve the required drug exposure for radiosensitization.