EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Metabolism of n methyl containing anti tumor agents carbon 14 di oxide breath analysis after administration of carbon 14 labeled n methyl drugs formaldehyde and formate in mice



Metabolism of n methyl containing anti tumor agents carbon 14 di oxide breath analysis after administration of carbon 14 labeled n methyl drugs formaldehyde and formate in mice



Biochemical Pharmacology 30(11): 1245-1252



The 14CO2 content of the breath was analyzed after administration of the following N-14CH3 labeled drugs to mice: aminopyrine, hexamethylmelamine (HMM), pentamethylmelamine (PMM), procarbazine and caffeine. Except for aminopyrine, the 14CO2 exhalation rate plots declined monophasically with half lives [t1/2] of 91 min ([14C]-HMM), 97 min ([14C]-PMM), 68 min ([14C]procarbazine) and 92 min ([14C]caffeine). The 14CO2 exhalation rate peaked rapidly after aminopyrine administration and declined bi-phasically with an initial t1/2 of 15 min and a terminal t1/2 of 126 min. The 14CO2 plots after both [14C]-HMM and [14C]amiopyrine were influenced by pre-treatment of mice with proadifen. Pretreatment with phenobarbitone shortened the t1/2 of the 14CO2 appearance rate after [14C]HMM by 24% but did not change the 14CO2 curve after administration of [14C]aminopyrine. The 14CO2 exhalation rate plots after administration of H14CHO and H14COOH were virtually identical with that obtained after [14C]aminopyrine and not influenced by either proadifen or phenobarbitone pretreatment. The 14CO2 exhalation rate profile obtained on metabolism of [14C]aminopyrine in mice thus appears to be determined by the rate of the oxidation of formaldehyde or formate to CO2. Only 24% of the label injected with the N-methyl moieties of [14C]HMM and 21% of the label in [14C]procarbazine were exhaled as 14CO2; 49% of the N-14CH3 in [14C]aminopyrine were metabolized to 14CO2. It remains to be determined whether this difference and the difference in the shapes of the 14CO2 exhalation profiles obtained with the cytotoxic N-14CH3 drugs as compared to [14C]aminopyrine, are related to the biochemical processes mediating their antineoplastic activity.

(PDF emailed within 1 workday: $29.90)

Accession: 005884634

Download citation: RISBibTeXText



Related references

Studies of the metabolism of N-methyl containing anti-tumour agents: 14CO2 breath analysis after administration of 14C-labelled N-methyl drugs, formaldehyde and formate in mice. Biochemical Pharmacology 30(11): 1245-1252, 1981

Comparison of the rates of expired carbon 13 labeled carbon di oxide following administration of carbon 13 labeled methoxy phenacetin and carbon 13 labeled di methyl aminopyrine to smokers and nonsmokers and the effect of hepatic alterations on expired carbon 14 labeled carbon di oxide kinetics following carbon 14 labeled methoxy phenacetin to rats. Clinical Research 28(2): 541A, 1980

Output of carbon 14 labeled carbon di oxide in breath after oral administration of carbon 14 methyl aminopyrine in hepatitis cirrhosis and hepatic bilharziasis its relationship to aminopyrine pharmaco kinetics. European Journal of Clinical Pharmacology 13(3): 223-230, 1978

Urinary excretion of 3 methyladenine and 1 methylnicotinamide by rats following administration of methyl carbon 14 methyl methanesulfonate and comparison with administration of carbon 14 methionine or formate. Chemico-Biological Interactions 55(1-2): 225-234, 1985

Assessment of the flux of mitochondrial acetyl coenzyme a in liver and kidney by using the differential production of carbon 14 di oxide from tracers of 1 carbon 14 labeled 4 methyl 2 oxo valerate and 2 carbon 14 labeled 4 methyl 2 oxo valerate. Biochemical Journal 210(1): 265-268, 1983

Continuous breath analysis of carbon 14 carbon di oxide carbon 12 carbon di oxide from carbon 14 formaldehyde and propionate for detection of vitamin b 12 deficiency. Journal of Nuclear Medicine 16(6): 553-554, 1975

Breath analysis of carbon 13 carbon di oxide following n demethylation of carbon 13 di methyl aminopyrine a measure of liver microsomal function. Gastroenterology 69(3): 865, 1975

The distribution of carbon 14 di methyl nitrosamine in mice auto radiographic studies in mice with inhibited and noninhibited di methyl nitrosamine metabolism and a comparison with the distribution of carbon 14 formaldehyde. Toxicology and Applied Pharmacology 45(2): 565-576, 1978

Synthesis of tetra methyl carbon 14 labeled penta methyl melamine 6 a new anti tumor agent. Journal Of Labelled Compounds & Radiopharmaceuticals: 779-784, 1983

Oxidation of n methyl and s methyl groups to formate and carbon di oxide in rat liver mitochondria. Federation Proceedings: 590, 1975

Significance of formate as an intermediate in the oxidation of the methionine s methyl l cysteine and sarcosine methyl carbons to carbon di oxide in the rat. Journal of Nutrition 107(9): 1665-1676, 1977

A kinetic evaluation of carbon 14 di oxide in expired air after carbon 14 labeled methacetin administration in rats used for the in vivo study of the metabolism of drugs. European Journal of Drug Metabolism & Pharmacokinetics 9(2): 161-168, 1984

Syntheses of labeled compounds synthesis of n alpha methyl tryptophane beta carbon 14 nitrogen 15 methyl 14 and n omega methyl tryptamine 1 carbon 14 nitrogen 15 methyl 14. Zeitschrift fuer Chemie 9(2): 64-65, 1969

Lithiated intermediates in the synthesis of carbon 11 labeled compounds the preparation of carbon 11 labeled d l alpha methyl ornithine and carbon 11 labeled d l alpha methyl valine. International Journal of Applied Radiation & Isotopes 35(6): 559-562, 1984

Synthesis and characteristics in tumor-bearing mice of N-(carbon-11) methyl-1-deoxynojirimycin and N-(carbon-11) methyl-1-deoxymannojirimycin. Nuclear Medicine and Biology 20(7): 843-847, 1993