Disease relevance of Zimeldine

• However, zimeldine was withdrawn from the market because of serious toxicity [1].
• This further strengthens the impression that the mechanism for the hypersensitivity syndrome induced by zimeldine does not seem to be related primarily to the 5-HT reuptake inhibition as such [2].
• Guillain-Barré syndrome following zimeldine treatment [3].
• Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats [4].
• 4. The 5-HT uptake inhibitor zimeldine (10 mg kg(-1)) had no effect on MDMA-induced hyperthermia [5].

Psychiatry related information on Zimeldine

• Overall, there was no significant effect of zimeldine on memory or reaction time measures as compared with placebo [6].
• Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures [6].
• To study the relationship between neonatal antidepressant administration, active (REM) sleep and adult alcohol-related behavior, rat pups were treated daily with 5 mg/kg desipramine (DMI) or 25 mg/kg zimeldine SC from the 6th to the 19th postnatal days [7].
• 5 An enhanced hypothermic response was also seen following repeated administration of zimeldine, mianserin or desipramine (all 10 mg kg-1 daily for 14 days) or repeated electroconvulsive shock (ECS; 5 ECS over 10 days) 24 h after the last treatment [8].
• After administration of zimeldine in combination with 5-HTP there was an increase in synchronized waking (W-2), followed by an increase in slow wave sleep (SWS), at first SWS-1 with spindles and then highly synchronized SWS-2 [9].

High impact information on Zimeldine

• Oral administration of the monoamine reuptake inhibitors sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), or zimeldine (10 mg/kg) for 10 days decreased the total number of beta-adrenoceptors present in rat cortex [10].
• The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z) [11].
• Decreasing 5-HT2 function by twice-a-day injection of 5 mg/kg of zimeldine or desipramine (DMI) produced 50% (p less than 0.01) and 56% (p less than 0.01), respectively, reductions in head-twitch behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)[12]
• Our findings indicate that alterations in central and peripheral serotoninergic function by a serotonin reuptake blocker (zimeldine) are unaccompanied by measurable changes in memory and/or reaction time in patients presumed to have Alzheimer's disease [6].
• The effects of zimeldine, its metabolites norzimeldine and CPP 200 as well as of the antidepressants clomipramine, imipramine and maprotiline on in vitro immune response were tested [4].

Chemical compound and disease context of Zimeldine

• The effects of zimeldine and alaproclate combined with a small dose of 5-HTP on waking and sleep stages in cats [9].
• The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III) [13].
• It was found that paroxetine and zimeldine at doses of 1-18 mg/kg dose-dependently prolonged waking and shortened slow-wave sleep and paradoxical sleep [14].
• 3) Presynaptic 5-HT1A-mediated hypothermia is attenuated by chronic treatment with amitriptyline, desipramine, zimeldine, high dose mianserin, tranylcypromine, lithium and repeated electroconvulsive shock (ECS) [15].

Biological context of Zimeldine

• At the age of 70 days, the zimeldine-treated rats expressed a selective increase of some components of activity in the open field test, and the DMI rats had a higher defecation score compared to the controls [7].
• Repeated oral doses of zimeldine (20 mg kg-1 per day, 14 days) also decreased the head-twitch response and the number of 5-HT2 binding sites and these effects persisted after 48 h withdrawal [16].
• Other compounds which inhibit the uptake of 5-HT such as fluoxetine, citalopram, norzimeldine, zimeldine and the non-tricyclic antidepressant, iprindol, did not enhance the cholinergic agonist induced tremor or salivation under the same conditions as did alaproclate [17].
• The present investigation was therefore designed to directly examine the effects of zimeldine on food intake [18].
• The therapeutic efficacy, tolerability and pharmacokinetics of zimeldine in elderly depressed patients were evaluated after administration of different doses of the drug in once daily evening doses [19].

Anatomical context of Zimeldine

• The action of several drugs on induced T cell secretion of IFN-gamma suggests that the mechanisms for the suppressive effect of zimeldine and norzimeldine on EAN symptoms can be due to an action on myelin T cell autoreactivity [4].
• Imipramine increased the concentration of NPY-LI in the hypothalamus by 65% while zimeldine was without effect [20].
• Lymphocyte transformation test (LTT) was applied to 28 patients who had developed a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug zimeldine [21].
• Fifty-four compounds structurally related to zimeldine or alaproclate and eight reference substances were examined as inhibitors of the high affinity binding of [3H]paroxetine to rat cerebral cortical membranes as a measure of the affinity of the 5-hydroxytryptamine (5-HT) transporter [22].
• Thus, opposite stereoselectivity for zimeldine N-oxygenation occurs in rat liver and hog liver microsomes [23].

Associations of Zimeldine with other chemical compounds

• Sleep, waking and EEG power spectra were studied in cats for 15 h following peroral administration of placebo or 10 mg/kg and 20 mg/kg of the 5-HT reuptake inhibitors zimeldine and alaproclate [24].
• Thus, ritanserin did not block the initial waking effect seen after zimeldine administration, indicating that this waking effect was not due to 5-HT2 stimulation [25].
• QSAR analysis of the zimeldine series of compounds indicates that substitution of halogens of the 2-position of the phenyl ring is unfavourable [22].
• Sleep/waking and EEG power spectra were investigated for 6 h periods in rats following administration of the essential amino acid L-tryptophan (40 mg/kg), the selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a combination of L-tryptophan and zimeldine [26].
• Thiobenzamide and methimazole significantly inhibit N-oxide formation whereas heat pretreatment of microsomes completely abolishes N-oxide formation, strongly suggesting that zimeldine N-oxygenation if solely dependent on the flavin-containing monooxygenase [23].

Gene context of Zimeldine

• Mouse, rat, dog and monkey brain MAO-B activities were inhibited by zimeldine more potently than MAO-A activity [27].
• 6. MAO-B was inhibited by the following drugs (in ascending order of potency): nortriptyline, imipramine, maprotiline, amitriptyline, zimeldine, nomifensine, and viloxazine [28].
• Stereoselective N-oxygenation of zimeldine and homozimeldine by the flavin-containing monooxygenase [23].
• Six patients with Obsessive-Compulsive Disorder (DSM III) were treated in an open uncontrolled trial with Zimeldine, for 8 weeks [29].
• After 3 weeks of treatment with zimeldine 5-HIAA and HMPG in CSF decreased significantly while HVA in CSF increased significantly [30].

Analytical, diagnostic and therapeutic context of Zimeldine

• Neuropsychological and neurochemical effects of zimeldine, a relatively specific serotonin reuptake blocker, were examined in four patients with clinically diagnosed Alzheimer's disease, in a double-blind, placebo-controlled, crossover study [6].
• The influence of the selective serotonin (5-HT) reuptake inhibiting antidepressant zimeldine and its metabolite norzimeldine was tested on experimental allergic neuritis (EAN) in Lewis rats, which is an animal model of the Guillain-Barré syndrome (GBS) in man [4].
• Furthermore, the zimeldine-rats responded with a decrease in ambulation in the open field to an alcohol dose which generally stimulates locomotion in rats [7].
• EEG slow wave activity was increased following zimeldine [24].
• Zimeldine versus amitriptyline in endogenous depression. A double-blind study with special reference to effects on liver function [31].

References