Desipramine and amphetamine metabolism

Consolo, S.; Dolfini, E.; Garattini, Silvio; Valzelli, L.

doi:10.1111/j.2042-7158.1967.tb08080.x

Cited by 63 publications

(5 citation statements)

References 8 publications

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“…Similar to the approach of using DA and 5HT transport blockers, the NE transport blocker desmethylimipramine (DMI) might be used to block m-AMPH-induced cortical NE overflow. However, as an inhibitor of p-hydroxylation of AMPH (Consolo et al, 1967;Sulser et al, 1966), DMI has been shown to significantly elevate AMPH levels in the rat brain (Dolfini et al, 1969). Because NE terminals are largely resistant to m-AMPH-induced injury (Brunswick et al, 1992;Seiden and Ricaurte, 1987), no independent measure is available to assess the effectiveness of DMI in blocking m-AMPH's effects on NE terminals.…”

Section: Discussionmentioning

confidence: 99%

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Eisch

Marshall

1998

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104

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Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro-Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 +/- 0.10 degrees C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4 degrees C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37 degrees C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m-AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m-AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.

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Section: Discussionmentioning

confidence: 99%

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Eisch

Marshall

1998

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104

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“…Pretreatment of several species with DMI has been shown to potentiate the central excitatory effects of amphetamine (Carlton, 1961;Stein, 1964;Dolfini, Tansella, Valzelli & Garattini, 1969). The potentiated effects of amphetamine are not related necessarily to inhibition of the reuptake mechanism by DMI, as the antidepressant drugs also inhibit the in vivo hydroxylation of amphetamine, thus increasing the amount of unmetabolized amphetamine in the brain (Consolo, Dolfini, Garattini & Valzelli, 1967;Lewander, 1969). However, the mouse does not metabolize amphetamine by hydroxylation and in this species DMI does not increase the concentration of amphetamine in the brain, nor does it potentiate amphetamine-induced excitation (Dolfini et al, 1969).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Pargyline and Desmethylimipramine on Monoamine Concentrations and Amphetamine‐induced Glycogenolysis in the Mouse Brain

Hutchins

1979

British J Pharmacology

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1 Pargyline (100 mg/kg) increased the concentration of cerebral noradrenaline dopamine and 5-hydroxytryptamine in the mouse. Amphetamine (5 mg/kg) reduced the concentration of noradrenaline and increased the concentrations of 5-hydroxytryptamine and dopamine. 2 When amphetamine was administered 4 h after an injection of pargyline, the effect of the sympathomimetic drug on the concentrations of noradrenaline and 5-hydroxytryptamine was not altered. The effect on the dopamine content was reversed, amphetamine causing a decrease instead of an increase. 3 Pargyline increased the concentration of cerebral glycogen, whereas amphetamine caused a decrease. 4 The administration of amphetamine 4 h after pargyline resulted in a decrease in brain glycogen similar to that seen after amphetamine alone. 5 These results suggest that the potentiation of the effect of amphetamine on animal behaviour by pretreatment with an inhibitor of monoamine oxidase is not mediated through a central action on noradrenaline release.6 Amphetamine-induced glycogenolysis was antagonized by 71% by desmethylimipramine (10 mg/kg). 7 The change in glycogen concentration as a function of time after an injection of amphetamine was not modified when 2 consecutive doses of amphetamine were given with an interval between doses of 30 minutes.

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“…In rats the depletion of brain and heart NA is partly due to the incorporation into the NA storage granules of a metabolite of amphetamine, p-hydroxynorephedrine, as a false transmitter ( GOLDSTEIN & ANACNOSTE 1965;THOENEN et al 1966;GROPPET~ & COSTA 1969a;LEWANDER 1970LEWANDER & 1971aBRODIE 1970;COSTA & GROPPETTI 1970). However, amphetamine caused NA depletion even in rats pretreated with desmethylimipramine (LEWANDER 1968b & 1971a; GROPPETTI & COSTA 1969a), a drug which inhibits p-hydroxylation of amphetamine in rats ( CONSOLO et al 1967;LEWANDER 1968b). In guinea pigs amphetamine is not p-hydroxylated (DRING et al 1970;present study) and p-hydroxynorephedrine (or norephedrine) could not be detected in the guinea pig brain and heart tissues in agreement with GROPPE~TI & COSTA (1969b).…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute and Chronic Amphetamine Intoxication on Brain Catecholamines in the Guinea Pig*

Lewander

1971

Acta Pharmacologica et Toxicologica

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A bstract: The effects of amphetamine on central and peripheral catecholamines have been studied in guinea pigs, since in this species, unlike several others, amphetamine is not metabolized by p-hydroxylation. Twenty mg/kg of dl-amphetamine-sulphate given intraperitoneally caused a 40 % decrease in brain and heart noradrenaline, a 13 % decrease in brain dopamine and a 60 % decrease in homovanillic acid in the caudate nucleus, four hours after its administration. The changes in tissue catecholamine levels and the increase in motor activity followed the time-course of the amphetamine concentrations both in the brain and plasma. After chronic administration of amphetamine at 12 hourly intervals for 7 or 18 days, there was a further decrease in brain and heart catecholamine and homovanillic acid levels. A 4-fold increase in the 3-0-methylated metabolites of noradrenaline and dopamine in brain after the administration of amphetamine to guinea pigs pretreated with nialamide and an increase in the urinary excretion of NA (13-fold) and adrenaline (3-fold) provided evidence for an amphetamine induced release of central and peripheral catecholamines as has previously been reported in rats and cats. Amphetamine disappeared from brain and plasma with an apparent half-life of 2.5-3.1 hours. Only amphetamine and hippuric acid were recovered in the urine after the administration of radioactively labelled amphetamine. No p-or (3-hydroxylated metabolites of amphetamine were present in the brain or heart tissues in the guinea pig. The results show that acute and chronic amphetamine administration cauSes changes in endogenous catecholamines in guinea-pigs similar to those found previously in rats in spite of differences in the metabolism of amphetamine between the two species.

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Desipramine and amphetamine metabolism

Cited by 63 publications

References 8 publications

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

The Effect of Pargyline and Desmethylimipramine on Monoamine Concentrations and Amphetamine‐induced Glycogenolysis in the Mouse Brain

Effects of Acute and Chronic Amphetamine Intoxication on Brain Catecholamines in the Guinea Pig*

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