Differences in teratogenic and toxic properties of alcohol dehydrogenase inhibitors pyrazole and 4-methylpyrazole in Drosophila melanogaster: I. ADH allozymes in variable genetic backgrounds. 1995

K T Eisses
Department of Plant Ecology and Evolutionary Biology, Utrecht University, The Netherlands.

Pyrazole and 4-methylpyrazole (4-MP) are effective inhibitors of alcohol dehydrogenase (ADH) activity in mammals both in vivo and in vitro. 4-MP has a tenfold higher inhibition specificity compared with pyrazole. Pyrazole proved a teratogenic compound in Drosophila melanogaster. Treatment of third instar larvae of D. melanogaster with pyrazole, in contrast with 4-MP, produced an increase in the number of dorsocentral and scutellar macrochaetae and wing-notches in the adult fly. A large difference in the penetrance of terata in males and females was observed. Similar effects were observed in flies lacking ADH molecules. The teratogenicity of pyrazole must be due to disturbance of processes other than ADH inhibition. Synergistic effects were observed between pyrazole and methoxyacetic acid (MAA), an in vitro inhibitor of sarcosine dehydrogenase activity. Each of these compounds, when fed to early third instar larvae, produced terata resembling the Notch mutant of D. melanogaster.

UI MeSH Term Description Entries
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D008297 Male Males
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D004331 Drosophila melanogaster A species of fruit fly frequently used in genetics because of the large size of its chromosomes. D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260 Female Females
D000077604 Fomepizole A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL. 4-Methylpyrazole,4-Methylpyrazole Monohydrochloride,Antizol,4 Methylpyrazole,4 Methylpyrazole Monohydrochloride
D000085 Acetates Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure. Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid
D000426 Alcohol Dehydrogenase A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen. Alcohol Dehydrogenase (NAD+),Alcohol Dehydrogenase I,Alcohol Dehydrogenase II,Alcohol-NAD+ Oxidoreductase,Yeast Alcohol Dehydrogenase,Alcohol Dehydrogenase, Yeast,Alcohol NAD+ Oxidoreductase,Dehydrogenase, Alcohol,Dehydrogenase, Yeast Alcohol,Oxidoreductase, Alcohol-NAD+
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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