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Toxicol Appl Pharmacol. 2019 May 14;378:114592. doi: 10.1016/j.taap.2019.05.011. [Epub ahead of print]

Comparative disposition of dimethylaminoethanol and choline in rats and mice following oral or intravenous administration.

Author information

1
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States of America.
2
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States of America.
3
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States of America. Electronic address: waidyanathas@niehs.nih.gov.

Abstract

Dimethylaminoethanol (DMAE) and its salts have been used to treat numerous disorders in humans and hence safety of its use is a concern. DMAE is a close structural analog of choline, an essential nutrient. Exposure to DMAE may affect choline uptake and synthesis. The current investigation characterizes: 1) the absorption, distribution, metabolism, and excretion (ADME) of DMAE in Wistar Han rats and B6C3F1 mice following a single gavage or intravenous (IV) administration of 10, 100 or 500 mg/kg [14C]DMAE, and 2) the ADME of [14C]choline (160 mg/kg) and the effect on its disposition following pre-treatment with DMAE (100 or 500 mg/kg). In both rats and mice, following gavage administration, DMAE was excreted in urine (16-69%) and as exhaled CO2 (3-22%). The tissue retention was moderate (21-44%); however, the brain concentrations were low and there was no accumulation. Serum choline levels were not elevated following administration of DMAE. The DMAE metabolites in urine were DMAE N-oxide and N,N-dimethylglycine; the carcinogen, N-N-dimethylnitrosamine, was not detected. The pattern of disposition of [14C]choline following gavage administration was similar to that of [14C]DMAE. Prior treatment with DMAE had minimal effects on choline disposition. The pattern of disposition of [14C]DMAE and [14C]choline following IV administration was similar to gavage administration. There were minimal dose-, sex- or species-related effects following gavage or IV administration of [14C]DMAE or [14C]choline. Data from the current study did not support previous reports that: 1) DMAE alters choline uptake and distribution, or 2) that DMAE is converted into choline in vivo.

KEYWORDS:

Choline; Dimethylaminoethanol; Disposition; Metabolism; N-N-dimethylnitrosamine; Tissue distribution

PMID:
31100288
DOI:
10.1016/j.taap.2019.05.011

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