Disease relevance of Norzimeldine

• Zimelidine and norzimelidine were tested for their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (1-16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice [1].
• Influence of renal failure on the kinetics of zimeldine and norzimelidine [2].

Psychiatry related information on Norzimeldine

• Plasma levels of zimelidine and norzimelidine in endogenous depression [3].
• Conversely, blood concentrations of zimelidine and its metabolite norzimelidine were also relatively unaffected by alcohol consumption [4].

High impact information on Norzimeldine

• Moreover, alaproclate, norzimelidine, and fluvoxamine all competitively displace [3H]imipramine from platelet plasma membranes [5].
• E decreased the rate of biotransformation of Z to norzimelidine (NZ) by 46%, but the AUCs of Z, NZ, and their total concentration over 8 hr were not altered by E [6].
• Steady-state concentrations of a new antidepressant, zimelidine (ZIM), and its active metabolite, norzimelidine (NZIM), were measured in plasma and cerebrospinal fluid (CSF) in eight depressed patients [7].
• Norzimeldine displaced the binding of [3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 microM [8].
• The bioassay, based on the use of one single, low concentration of serotonin, was found to be very sensitive and to have a high reliability (coefficient of variation about 2% as calculated from duplicate samples), and to correlate highly with log plasma concentration of zimelidine, norzimelidine, and of desipramine [9].

Biological context of Norzimeldine

• Zimelidine and norzimelidine protein binding measured by equilibrium dialysis and cerebrospinal fluid [7].
• A low concentration of norzimelidine can be used to selectively measure the rate of dissociation of [3H]imipramine from high-affinity binding sites in the mouse cerebral cortex [10].
• Pharmacokinetics of zimelidine. Systemic availability of zimelidine and norzimelidine in human volunteers [11].
• Thus, the bioavailability of zimeldine and of its active metabolite norzimeldine is unaffected by food intake, suggesting that the drug need not be taken in a strictly defined relation to meals [12].
• The possible influence of concomitant food intake on the bioavailability of the novel antidepressant zimeldine and its active metabolite norzimeldine was assessed in ten healthy female volunteers, who ingested a single dose of 200 mg zimeldine on an empty stomach and together with a standardized breakfast of 1 840 kJ [12].

Anatomical context of Norzimeldine

• Specific binding in the hypothalamus was inhibited in a stereoselective manner by the stereoisomers of norzimelidine [13].
• Zimelidine, mainly via its metabolite norzimelidine, caused a pronounced inhibition of uptake of 14C-5-HT in platelets, decrease in whole blood 5-HT and inhibition of accumulation of 14C-5-HT in rat hypothalamic synaptosomes incubated in the patients plasma [14].
• The concentration in blood plasma of zimelidine should probably reach a minimum level of 250 nmol/l and norzimelidine 500 nmol/l, and to achieve this a general dosage of 100 mg b.i.d. is recommended [15].
• Zimeldine and its metabolites norzimeldine and CPP 200 all induced statistically significant increased [3H]thymidine incorporation in cultured lymphocytes from the HSS patients compared with the controls, norzimeldine being the most potent inducer [16].

Associations of Norzimeldine with other chemical compounds

• The ability of four antidepressant drugs, imipramine, alaproclate, norzimelidine, and fluvoxamine, to inhibit serotonin transport into platelet plasma membrane vesicles was tested over a range of external Na+ concentrations [5].

Gene context of Norzimeldine

• At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug [17].
• The accumulation and deamination of 14C-tryptamine by mouse brain slices or homogenates of rat hypothalamus were not inhibited by cocaine or norzimelidine, a selective inhibitor of the neuronal 5-HT uptake [18].

Analytical, diagnostic and therapeutic context of Norzimeldine

• A specific, sensitive, rapid and reproducible analytical method for zimelidine [3-(4-bromophenyl)-N,N-dimethyl-3(3-pyridyl)allylamine] and its biologically active demethylated metabolite, norzimelidine, in human plasma was developed using gas-liquid chromatography (GLC) with loxapine as the internal standard [19].
• Quantitation of zimelidine and norzimelidine in plasma using high-performance liquid chromatography [20].
• The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration [21].

References