Papierchromatographischer Nachweis von Stoffwechselprodukten des Tofranil

Herrmann, Bernhard G.; Schindler, W.; Pulver, R

doi:10.1159/000134824

Cited by 11 publications

(4 citation statements)

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“…The main metabolic pathways were reported to be N-demethylation, N-oxidation and C-hydroxylation following glucuronide formation (12,13,14,15,16,17).…”

Section: Discussionmentioning

confidence: 99%

Urinary excretion of conjugates of dothiepin and northiaden (mono- N-demethyl-dothiepin) after an oral dose of dothiepin to humans

Kawahara

Awaji

Uda

et al. 1986

European Journal of Drug Metabolism and Pharmacokinetics

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Only small amounts of unconjugated dothiepin (unchanged drug) and northiaden were excreted in urine over a 72 hr period. More than 10% of the dose was excreted as conjugated dothiepin and less than 0.8% of the dose as conjugated northiaden. Conjugated dothiepin was thus found to be an important metabolite of dothiepin. Conjugated dothiepin and northiaden were hydrolyzed with beta-glucuronidase, and their hydrolysis inhibited with 1,4 saccharolactone. Conjugated dothiepin and northiaden were found to be a quaternary ammonium-linked glucuronide and a tertiary N-glucuronide, respectively.

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“…The main metabolic pathways were reported to be N-demethylation, N-oxidation and C-hydroxylation following glucuronide formation (12,13,14,15,16,17).…”

Section: Discussionmentioning

confidence: 99%

Urinary excretion of conjugates of dothiepin and northiaden (mono- N-demethyl-dothiepin) after an oral dose of dothiepin to humans

Kawahara

Awaji

Uda

et al. 1986

European Journal of Drug Metabolism and Pharmacokinetics

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“…Imipramine and desipramine are hydroxylated in the 2 and 10 positions (Herrmann & Pulver, 1960;Bickel, 1966;Crammer & Scott, 1966). Since desipramine is rapidly formed from imipramine but is slowly metabolized in rats (Dingell, Sulser & Gillette, 1964) it might be expected that a competitive inhibition with the hydroxylation of amphetamine would be effective in vivo for several hours.…”

Section: Discussionmentioning

confidence: 99%

Desipramine and amphetamine metabolism

Consolo

Dolfini

Garattini

et al. 1967

Journal of Pharmacy and Pharmacology

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Desipramine (2.5-5 mg/kg) increases the urinary excretion of amphetamine given intraperitoneally at doses of 75-15 mg/kg and it decreases the excretion ofp-hydroxyamphetamine. The rate of removal of brain amphetamine is decreased by desipramine (5 mg/kg, i.p.) when amphetamine is injected intraperitoneally but not when it is injected intracerebrally. It is suggested that desipramine impairs the hydroxylation of amphetamine in the liver thereby increasing the level of circulating amphetamine and eventually of brain amphetamine.MIPRAMINE and other tricyclic antidepressant agents are known to I increase and prolong the pharmacological effects of (+)-amphetamine showed that imipramine and desipramine prolong the hyperthermia induced by amphetamine in rats and that they also increase the amphetamine levels in brain and liver.These findings prompted an investigation to establish whether desipramine was able to affect the formation of p-hydroxyamphetamine, the major metabolite of amphetamine in rats (Axelrod, 1954a, b; Alleva, 1963; Dring, Smith & Williams, 1966). Materials and methodsMale Sprague-Dawley rats, 165 5 g, were kept in Makrolon cages at constant room temperature (22") and relative humidity (60%). (+)-Amphetamine sulphate and desipramine were injected intraperitoneally and the urines were collected 24 hr after dosing.Amphetamine and p-hydroxyamphetamine were determined in urine and amphetamine in brain by the method of Axelrod (1954 a, b). Free p-hydroxyamphetamine was determined in urines before acid hydrolysis. Suitable controls indicated that desipramine did not interfere with the determination of urinary amphetamine or p-hydroxyamphetamine. The brains of animals pretreated with desipramine (5 mg/kg i.p.) did not affect the recovery of (+)-amphetamine added in vitro.In some experiments (+)-amphetamine was introduced into the brain by the method of Valzelli (1964). Table 1 gives the results obtained on measuring amphetamine and p-hydroxyamphetamine in urines of rats treated with different doses of amphetamine alone or with desipramine. It is evident that desipramine treatment changed the pattern of amphetamine metabolism by increasing the urinary excretion of amphetamine and decreasing that of p-hydroxyamphetamine. Results

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“…Control 144.0 f 11.9 (9) 158.1 f 7.8 (9) 172.6 f 11.2 (7) 171.0 f 13.1 (8) 170 containing 4 ml of a 6% dextran7 solution was implanted subcutaneously, under light ether anesthesia and sterile conditions, on the back through a small incision in the sacral region 24 hr prior to imipramine administration (as described). The sac was removed after 30 min; the contents, pooled from three animals, were analyzed for imipramine (corresponding to the level of free drug).…”

Section: Methodsmentioning

confidence: 99%