Effect of nomifensine on motor activity, dopamine turnover rate and cyclic 3?, 5?-adenosine monophosphate concentrations of rat striatum

Gerhards, Hermann J.; Carenzi, A.; Costa, E.

doi:10.1007/bf00499104

Cited by 88 publications

(46 citation statements)

References 23 publications

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“…Amphetamine and its derivatives, in addition to their inhibitory activity on monoamine uptake, are acting mainly by promoting the release of catecholamines into the synaptic cleft (for refs, see Estler, 1975). The effects of nomifensine, however, on the catecholamine system, including the small increase in striatal DA turnover (Gerhards et al, 1974), are not caused by an enhancement of catecholamine release. Figure 5 shows the influence of nomifensine and Damphetamine on newly accumulated NA in hypothalamic synaptosomes.…”

Section: Resultsmentioning

confidence: 99%

“…Nomifensine is a new antidepressant drug with a pharmacological profile somewhat different from that of the classical tricyclic antidepressants (Hoffmann, 1973;Gerhards et aL, 1974). Previous studies with synaptosomes have shown that the most relevant effect of nomifensine seems to be the strong inhibition of NA and DA re-uptake (Hunt et al, 1974;Schacht & Heptner, 1974).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Studies on brain metabolism of biogenic amines.

Schacht¹,

Leven²,

Bäcker³

1977

Brit J Clinical Pharma

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Studies on brain metabolism of biogenic amines.

Schacht¹,

Leven²,

Bäcker³

1977

Brit J Clinical Pharma

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“…Many of the diverse and often unique behavioural (Anden, 1970;Snyder et al, 1974;Ross & Kelder, 1979), electrophysiological Sanghera et al, 1979) and pharmacological (Gerhards et al, 1974;Braestrup, 1977;Ross, 1977;Ross & Kelder, 1979) characteristics of psychostimulants are not adequately explained by their broad classification into amphetamine-[drugs that primarily release dopamine (DA)] and non-amphetamine-like (drugs that inhibit DA reuptake) substances. Many of the biochemical changes produced by amphetamine in the DA terminal regions are not similarly produced at the cell bodies (Elverfors & Nissbrandt, 1992).…”

Section: Introductionmentioning

confidence: 99%

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Karoum

Chrapusta

Brinjak

et al. 1994

British J Pharmacology

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1 The effects of single-dose regimens of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine (DA) release and metabolism were evaluated in the frontal cortex, hypothalamus, nucleus accumbens and striatum. The regimens selected are known to produce substantial behavioural effects. 2 3-Methoxytyramine (3MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used to assess DA metabolism by catechol-O-methyltransferase and monoamine oxidase respectively. The rate of formation of 3MT was used as an index of synaptic DA. The ratio and sum, respectively, of 3MT and DOPAC rates of formation were used to assess DA reuptake inhibition and turnover. 3 The effects of amphetamine on 3MT production and DOPAC steady-state levels were similar in all regions, suggesting similar pharmacodynamic actions. Amphetamine increased 3MT formation and steady-state levels, and reduced DOPAC steady-state levels. DOPAC formation was significantly reduced only in the nucleus accumbens and striatum. Total DA turnover remained unchanged except in the nucleus accumbens. Apparently, the amphetamine-induced increase in DA release occurred at the expense of intraneuronal DA metabolism and did not require stimulation of synthesis. 4 Nomifensine elevated 3MT formation in all regions. A similar effect was produced by cocaine except in the nucleus accumbens. GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens. 5 Cocaine selectively reduced DOPAC formation in the frontal cortex. Nomifensine increased and reduced, respectively, DOPAC formation in striatum and hypothalamus. GBR 12909 elevated DOPAC formation in all regions except the cortex, where pargyline did not reduce DOPAC levels in GBR 12909-treated rats. 6 Ratios and sum of 3MT and DOPAC rates of formation also exhibited wide regional variations for each drug. In contrast to the other drugs, the ratio was not increased after GBR 12909. Apparently, the DA uptake properties of this drug are poorly related to its in vivo effects on the ratio of 3MT production to that of DOPAC, which should increase when DA reuptake is inhibited. 7 Total DA turnover was increased by GBR 12909 in the hypothalamus, nucleus accumbens and striatum, while cocaine and nomifensine increased it only in the nucleus accumbens and striatum respectively. 8 It is concluded that: (a) 3MT and DOPAC rates of formation provide better indices of DA release and metabolism than do their steady-state concentrations. (b) Some effects of DA uptake blockers on DA transmission, especially those of nomifensine and cocaine, may be attributed to increased DA release. (c) Patterns of regional effects of psychostimulants on the dynamics of DA release and metabolism may be better biochemical correlates of stimulant-induced behaviours than would changes in any single region.

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“…Nomifensine, an effective blocker of dopamine uptake (Hunt, Kannengiesser & Raynaud, 1974), produced at the higher dose level (20 mg/kg) an increase in both homovanillic acid (Gerhards, Carenzi & Costa, 1974 and Table 3) and p-tyramine (Table 3). These results are surprising because they are at variance with those obtained after other treatments that increase dopamine turnover (see review by Juorio, 1982a).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Amfonelic Acid and Some Other Central Stimulants on Mouse Striatal Tyramine, Dopamine and Homovanillic Acid

Juorio¹

1982

British J Pharmacology

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1 The concentrations of p-and m-tyramine, dopamine and homovanillic acid were measured in the mouse striatum following the subcutaneous administration of amfonelic acid, (+)-amphetamine or nomifensine.2 The administration of 2.5-25 mg/kg of amfonelic acid produced a reduction in p-tyramine that lasted at least 8 h. m-Tyramine was significantly increased and this was observed between 2 and 24 h after drug treatment. The levels of homovanillic acid were increased within 4 h after amfonelic acid administration.3 (+)-Amphetamine treatment (5 mg/kg) produced a reduction in p-tyramine observed up to 4 h after its administration and no significant changes in m-tyramine. 4 The administration of 10 mg/kg of nomifensine produced no significant changes in p-tyramine, m-tyramine or homovanillic acid. By increasing the dose to 20 mg/kg, nomifensine produced an increase in p-tyramine and homovanillic acid. 5 The present results support the view that amfonelic acid and (+)-amphetamine would respectively release granular or newly synthesized dopamine, both actions being accompanied by an increase in tyrosine hydroxylase activity and dopamine turnover which in turn reduces p-tyramine but produces no change or an increase in m-tyramine.6 The effects of nomifensine were observed after the administration of a relatively high dose (20 mg/kg), that was lethal to some mice (about 20%, at 2 h), and more likely to possess unspecific actions.

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Effect of nomifensine on motor activity, dopamine turnover rate and cyclic 3?, 5?-adenosine monophosphate concentrations of rat striatum

Cited by 88 publications

References 23 publications

Studies on brain metabolism of biogenic amines.

Studies on brain metabolism of biogenic amines.

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

The Effects of Amfonelic Acid and Some Other Central Stimulants on Mouse Striatal Tyramine, Dopamine and Homovanillic Acid

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