Disease relevance of BRN 6064060

• The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia [1].
• We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies [1].
• Nomifensine-induced allergic reactions [2].
• Fatal necrotising vasculitis associated with nomifensine [3].
• Nomifensine, acute hemolytic anemia, and renal failure [4].

Psychiatry related information on BRN 6064060

• With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration [5].
• Nomifensine exacerbates narcolepsy [6].
• Efficacy of nomifensine in different depressive syndromes [7].
• A review of pharmacodynamic studies of nomifensine in healthy subjects indicates that nomifensine caused neither negative nor positive (euphoric) mood alterations and led to no impairments in various tests of performance and to some improvement in vigilance, attention, and psychomotor performance [8].
• Nomifensine was at least as effective as imipramine in reducing depressive symptoms at average doses of 150 mg/day [9].

High impact information on BRN 6064060

• To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens [10].
• Additionally, 3H-dopamine release occurred in vitro through a Ca(2+)-dependent mechanism, as well as through reverse function of a nomifensine-sensitive dopamine transporter [11].
• Pharmacological protection of dopaminergic nerve terminals with nomifensine abolished MPTP-mediated phosphorylation and translocation of STAT3 and prevented induction of astrogliosis [12].
• 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively [13].
• Treatment of bulimia with nomifensine [14].

Chemical compound and disease context of BRN 6064060

• After addition of tetrodotoxin (40 microM) to the perfusion fluid or pretreatment with nomifensine (100 mg/kg, i.p.), exposure to hypoxia no longer increased the dopamine levels [15].
• However, 100 microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine [16].
• In CNic cultures, basal DA levels were also elevated (approximately 9x control), similar to that in CHox cultures; however, although acute hypoxia had a stimulatory effect on DA release (approximately 2x basal), nicotine, nomifensine, and high K+ were ineffective [17].
• Hypothermia induced by a high dose of apomorphine (16 mg/kg) is not antagonized by neuroleptics, but is strongly antagonized by antidepressants (imipramine-like drugs, amineptine, amoxapine, nomifensine, viloxazine) and potential antidepressants (beta-adrenergic stimulants) [18].
• In the treatment of Parkinsonism, nomifensine may be considered as an alternative to amantadine or anticholinergics, especially where depression is an added feature [19].

Biological context of BRN 6064060

• The pharmacokinetics of nomifensine were studied after single oral and intravenous doses [20].
• The AUC of free nomifensine decreased substantially (from 0.78 to 0.32 hr X mumol/L) and the elimination t1/2 was shortened (from 4.39 to 2.11 hours) after a 2-week dosing period [20].
• Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin [21].
• Kinetics and metabolism of nomifensine [22].
• Nomifensine, a DA reuptake inhibitor, rescued nearly 60-70% of the cells from DA- and DA plus KCN-induced apoptosis, suggesting that DA toxicity is in part mediated intracellularly [23].

Anatomical context of BRN 6064060

• The proteins of aged rat substantia nigra showed a significant increase of carbonyl groups following nomifensine treatment [24].
• Nomifensine was rapidly absorbed from the gastrointestinal tract [20].
• Nomifensine was extensively distributed in body fluids and tissues, with an apparent volume of distribution of 8.69 L/kg [20].
• Uptake inhibition by nomifensine (20 mg kg-1) caused an apparent 15-fold change in the value of Km in the nucleus accumbens, similar to results previously reported in the caudate-putamen [25].
• In the prefrontal cortex, cingulate cortex, striatum, and olfactory tubercle, nomifensine was found to increase 3-MT steady-state levels and accumulation rates [26].

Associations of BRN 6064060 with other chemical compounds

• Evaluation of individual patients showed that only one patient had a normal PRL response to either Nom or Dom, while the TSH response to the latter returned to normal in five of seven patients [27].
• The release evoked by 5-HT in the presence of 10 microM nomifensine (an antagonist of the DA transporter) was less than in its absence, but the difference between weaver and +/+ striatum remained [28].
• Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR-12909 (10-1,000 microM) or nomifensine (10-1,000 microM) dose-dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA [29].
• The uptake of [3H]5-hydroxytryptamine ([3H]5-HT) into synaptosomal preparations of substantia nigra was abolished by fluoxetine and reduced by desipramine, but was unaffected by nomifensine [30].
• In the bioavailability study, 24 men received single oral 50 mg doses of nomifensine maleate in a capsule or as an aqueous solution [31].

Gene context of BRN 6064060

• Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients [32].
• Since basal DA levels were low, the experiments were performed under local infusion of the reuptake inhibitor nomifensine (5 mumol/l), which increased extracellular DA levels 5-fold around the probe, but did not affect the occurrence of the nocturnal PRL surge on day 7-8 of PSP [33].
• The following serotoninergic drugs were perfused in the absence or presence of nomifensine (5 microM) or tetrodotoxin (TTX; 2 microM): clomipramine (10, 500 and 1,000 microM), a selective 5-HT reuptake inhibitor; 8-OH-DPAT (50 and 500 microM), a 5-HT1A receptor agonist; and alpha-methyl-5-HT (1, 5 and 50 microM), a 5-HT2 receptor agonist [34].
• Nomifensine administration had no appreciable effect on the TRH-induced release of TSH and prolactin [35].
• Some drugs elicit antibodies that react at specific sites on the cell membrane independently of drug (eg, nomifensine and the Rh antigens (E) or quinidine and platelet GPV) [36].

Analytical, diagnostic and therapeutic context of BRN 6064060

• Intravenous self-administration of nomifensine in rats: implications for abuse potential in humans [37].
• To determine the effect of tetrodotoxin (TTX), basal concentrations of DA in the SNR were first elevated threefold by including nomifensine (1 microM) in the nigral perfusion solution.(ABSTRACT TRUNCATED AT 250 WORDS)[38]
• We have studied the effect of the oral administration of 200 mg nomifensine (nom), a drug which activates the dopaminergic system, on GH and PRL secretion in 15 normal subjects, 18 patients with idiopathic hyperprolactinemia, and 17 patients with tumoral hyperprolactinemia [39].
• Nomifensine: diagnostic test in hyperprolactinemic states [40].
• The AUC of free nomifensine after oral dosing was only 26.5% of that after intravenous infusion [20].

References