Related Experiment Video

Updated: Aug 4, 2026

Preparation of Naringenin Solution for In Vivo Application
08:18

Preparation of Naringenin Solution for In Vivo Application

Published on: August 10, 2021

Biotransformation and some effects of 2-dimethylamino-4-(N-methylanilino)-phenol in dogs

H Gaber, M Kiese, G Renner

    Naunyn-Schmiedeberg'S Archives of Pharmacology
    |July 18, 1977
    PubMed

    Insights

    2-Dimethylamino-4-(N-methylanilino)-phenol (MP) rapidly metabolizes in dogs, forming a sulfuric acid ester and undergoing covalent binding. This active metabolite causes ferrihemoglobin formation, Heinz bodies, and hemolytic anemia.

    Area of Science:

    • Pharmacology and Toxicology
    • Biochemistry
    • Hematology

    Background:

    • 2-Dimethylamino-4-(N-methylanilino)-phenol (MP) is an active metabolite of N,N-dimethylaniline-N-oxide.
    • MP is involved in the autocatalytic formation of ferrihemoglobin.

    Purpose of the Study:

    • To investigate the metabolic fate and toxicological effects of MP in vivo.
    • To elucidate the chemical structure of MP's oxidation product.

    Main Methods:

    • Intravenous administration of 14C-labeled MP in dogs.
    • Analysis of blood, urine, and tissue for radioactivity and metabolites.
    • Spectroscopic analysis to determine the structure of MP oxidation products.

    Main Results:

    • MP rapidly disappeared from blood, with significant hemoglobin oxidation.
    • Major metabolites included the sulfuric acid ester of MP, methylamine, dimethylamine, and N-methylaniline.
    • MP induced ferrihemoglobin formation, Heinz bodies, hemolytic anemia, and kidney tubule necrosis at lethal doses.

    Conclusions:

    • MP undergoes rapid metabolism via sulfation, covalent binding, and hydrolysis in vivo.
    • The oxidation product of MP is a resonance hybrid of two quinonimine structures.
    • MP exhibits significant toxicity, leading to hematological and renal damage.

    More Related Videos

    Elucidating the Metabolism of 2,4-Dibromophenol in Plants06:54

    Elucidating the Metabolism of 2,4-Dibromophenol in Plants

    Published on: February 10, 2023

    Assessing Cytotoxicity of Metabolites of Typical Triazole Pesticides in Plants08:22

    Assessing Cytotoxicity of Metabolites of Typical Triazole Pesticides in Plants

    Published on: December 22, 2023

    Related Concept Videos

    Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

    Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

    Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
    Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
    Phase I Reactions: Reductive Reactions01:27

    Phase I Reactions: Reductive Reactions

    Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...
    Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

    Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

    Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...
    Phase II Reactions: Methylation Reactions01:17

    Phase II Reactions: Methylation Reactions

    Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
    The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
    Phase II Reactions: Miscellaneous Conjugation Reactions01:19

    Phase II Reactions: Miscellaneous Conjugation Reactions

    Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
    A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
    Toxicity Testing in Animals01:23

    Toxicity Testing in Animals

    Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...