Teratogenic and antiteratogenic effects of nicotinamide derivatives in chick embryos. 1982

E M Uyeki, and J Doull, and C C Cheng, and M Misawa

Teratogenic and antiteratogenic effects of nine nicotinamide analogs in chick embryos were investigated. Further, the teratisms of 6-aminonicotinamide (6-AN), nicotinamide analogs, and an organophosphate (diazinon) were compared. White leghorn chick embryos were used. Agents were injected into the yolk of eggs on d 3 of incubation. Morphological observations were made on d 17 of incubation. Chemical names for compounds I to IX are: I, 6-dimethylaminonicotinamide; II, 6-diethylaminonicotinamide; III, 6-methylamino-3-(N-methyl)-nicotinamide; IV, 6-dimethylamino-3-pyrimidine carboximide; V, 6-(dimethylamino)-nicotinic acid; VI, 6-chloro-3-[N-(5-diethylamino)-2-pentyl]-nicotinamide; VII, 6-mercaptonicotinamide; VIII, [N-acetyl-N'-(3-pyridyl)-carbonyl]-hydrazine; IX, nicotinamide 1-N-oxide. The LD50 values in mumol per egg were as follows: 6-AN, 0.073; compound II, 0.23; compound III, 1.11; compound I, 1.32; compound VI, about 3. Compounds IV, V, VII, VIII, and IX showed no toxicity or lethality at the highest doses tested (10 mumol/egg). Among the nine nicotinamide analogs, compounds I, II, and III, which have an amino group at the 6-position of the pyridine ring, were teratogenic. Their teratogenic signs were similar to those caused by 6-AN: they showed growth retardation, anteriorly directed short legs, and coarse, dense feathering. The teratogenic effects of compounds I, II, and III were prevented by pretreatment with nicotinamide, as were the effects of 6-AN and diazinon. Among the nine analogs, only compound VIII had an antiteratogenic effect against the diazinon-induced micromelia (in which the cardinal signs were tibiotarsal angulations and poor feathering). For teratisms produced by 6-aminonicotinamide analogs and organophosphates, nicotinamide was an effective antiteratogenic agent. However, some differences in the malformations induced by both types of agents were found. We suggest that the addition of a 3-acetylpyridine type to the nicotinamide-related teratisms (6-AN type, 3-acetylpyridine type, and organophosphate type) will provide a clearer distinction among the types.

UI MeSH Term Description Entries
D007928 Lethal Dose 50 The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population. LD50,Dose 50, Lethal
D009536 Niacinamide An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D003976 Diazinon A cholinesterase inhibitor that is used as an organothiophosphorus insecticide. Bazudine,Dimpylate,Neocidol,Neotsidol
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
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen

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