Effects Of Zimeldine Research Articles

Effect of zimeldine and its metabolites on [3H]thymidine incorporation in lymphocyte cultures from psychiatric patients with or without a hypersensitivity reaction during zimeldine therapy

Lymphocyte transformation test (LTT) was applied to 28 patients who had developed a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug zimeldine. Twenty-seven patients treated with zimeldine without any symptom of an HSS were matched controls. 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. The results indicate an immunoreactive process in the development of the HSS induced by zimeldine.

Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats

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. Zimeldine and norzimeldine both suppressed clinical signs of actively induced EAN when given at a dose of 20 mg/kg/day intraperitoneally via osmotic pumps. 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. Thereby we used an immunospot assay for interferon-gamma (IFN-γ) produced by lymph node mononuclear cells (MNC), which reflects number of memory T lymphocytes activated by antigen or lectin, in this experiment bovine peripheral nerve myelin (BPM) and phytohemagglutinin (PHA), respectively. In the IFN-γ secretion assay zimeldine, CPP 200, clomipramine and maprotiline all in a concentration-dependent mode reduced the number of IFN-γ secreting cells while norzimeldine and imipramine did not affect the IFN-γ secretion. In assays for proliferation in response to antigen or lectin, the concentration 10 −4 M was judged toxic for all substances tested, and at concentrations below that all but zimeldine showed a dose-dependent slight reduction of MNC proliferation. The action of several drugs on induced T cell secretion of IFN-γ 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. All the monoamine reuptake inhibiting antidepressants tested in this study showed immunomodulatory effects by either a reduction of the number of IFN-γ-secreting cells or the MNC proliferation. These observations call for further studies of immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of recognized autoimmune diseases.

Effects of zimeldine, a selective 5-HT reuptake inhibitor, combined with ritanserin, a selective 5-HT 2 antagonist, on waking and sleep stages in rats

Sleep and waking in rats were studied 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a selective 5-HT 2 antagonist (ritanserin) and a combination of ritanserin and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased the first 3 h, followed by an increase in deep slow wave sleep (SWS-2), maximal in hours 4 and 5. Ritanserin gave an increase in SWS-2 that was spread out over the recording period. Ritanserin + zimeldine also gave a biphasic effect as zimeldine did, and the initial increase in waking and the following increase in SWS-2 tended to be stronger. Thus, ritanserin did not block the initial waking effect seen after zimeldine administration, indicating that this waking effect was not due to 5-HT 2 stimulation. The increase in SWS-2 seemed to reflect an addition of the increases following the zimeldine and ritanserin alone conditions. This suggests that the increase in SWS-2 seen after 5-HT reuptake inhibition and 5-HT 2 blockade are independent phenomena. Zimeldine alone, ritanserin alone and the combination all gave a clear reduction of rapid eye movement sleep.

Serotonergic modulation of ingestive behavior in pigeons

The effects of peripheral administration of the serotonin agonist zimeldine and the serotonin antagonist cyproheptadine reduced the amount of feeling and and water consumption were evaluated in domestic pigeons. Injections of zimeldine reduced the amount of feeding and drinking dose-dependently in 24-hr fasted animals. Administration of cyproheptadine enhanced food and water consumption dose-dependently up to a dose of 160 μg per 100 g body weight in nondeprived pigeons. Higher doses reduced ingestion probably due to a general behavioral depression. The effect of zimeldine was antagonized by cyproheptadine. It is concluded that, as in mammals, serotonin participates as an inhibitor in the regulation of feeding in birds. Contrary to the situation in mammals it has no activating effect on drinking but leads to a reduction of water consumption in pigeons.

Effects of psychoactive drugs on delta sleep-inducing peptide concentrations in rat brain

The concentration of delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) in rat brain regions was determined by radioimmunoassay following treatment with various psychoactive drugs or adrenalectomy. The antidepressant drugs imipramine and zimeldine, given orally twice daily for three weeks, reduced the concentrations of DSIP-LI in the hypothalamus, frontal cortex and cerebellum. The effects of zimeldine were similar but somewhat less pronounced than those of imipramine. The neuroleptic drug haloperidol, given i.p. once daily for two weeks, increased the concentration of DSIP-LI in the hypothalamus, but not in the frontal cortex. A single dose of haloperidol did not affect the concentration of DSIP-LI in either region. Like haloperidol, pentobarbital elevated the concentration of DSIP-LI in the hypothalamus; however, this effect of the barbiturate was seen after single but not after repeated administration. Cortical concentrations of DSIP-LI were unaffected following both single and repeated pentobarbital administration. Finally, adrenalectomy increased the concentration of DSIP-LI in the hypothalamus, but not in the other brain regions. In conclusion, the DSIP concentration in rat brain regions may be altered by a variety of interventions. The most profound and general alterations were observed following administration of antidepressant drugs.

The effects of zimeldine and alaproclate combined with a small dose of 5-HTP on waking and sleep stages in cats

Sleep and waking stages in cats were studied 8 h following administration of zimeldine and alaproclate, in combination with saline or 5-hydroxy-1-tryptophan (5-HTP). Both drugs in combination with saline reduced rapid eye movement sleep and ponto-geniculo-occipital wave activity, and the effects were potentiated with 5-HTP. 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. The changes were interpreted as reflecting a serotonergic deactivating effect expressed by an electroencephalographic synchronizing effect. This is consistent with earlier studies following serotonin depletion and serotonin precursor loading. After alaproclate in combination with 5-HTP there were changes in W-2 and SWS-1 suggestive of the same process but much less pronounced. The difference between the two serotonin uptake inhibitors is interpreted as being due to regional differences in their uptake inhibition.

The effects of zimeldine on voluntary ethanol consumption: Studies on the mechanism of action

Research from our laboratory has shown that several specific serotonin uptake blockers (zimeldine, fluoxetine, sertraline) are effective in reducing voluntary ethanol consumption in rats. However, the mechanism of action of these drugs is not well understood. The series of experiments presented here examined whether zimeldine produces its effects on ethanol consumption via a serotonin mediated anorexic action. In addition the effects of chronic administration of zimeldine were examined in rats drinking a dextrose solution, as well as in ethanol-consuming animals following 5-HT depletion with p-chloroamphetamine. The results indicate that zimeldine reduces the consumption of ethanol, dextrose and saccharin solutions. However, these effects on fluid consumption are not blocked by prior serotonin depletion. The results are discussed in terms of serotonin's role in this process in general and the possibility that zimeldine's effects are not directly related to its capacity to block the reuptake of serotonin.

Effect of Zimeldine, a New Antidepressant, on the Forced Swimming Test in Rats

Effect of Zimeldine, a New Antidepressant, on the Forced Swimming Test in Rats

Effects of zimeldine and other antidepressants on skilled performance: a comprehensive review.

Existing data suggest that amitriptyline, doxepin, mianserin, viloxazine and imipramine impair the performance of skilled psychomotor tasks. The degree of impairment, as well as the degree of interaction with alcohol, is closely related to the sedative potency of the drug. the adverse effects on psychomotor skills are, however, mainly limited to the first 10 days of treatment. In contrast, nortriptyline, clomipramine, desipramine, protriptyline, nomifensine and zimeldine have much less marked effects on skilled performance. Despite its being a relatively new antidepressant, the effects of zimeldine on psychomotor skills have already been extensively investigated. It has been shown to be without stimulant or sedative effects, and there does not appear to be any additive effect between zimeldine and ethanol. The lack of detrimental effects on skills related to such tasks as driving, makes zimeldine suitable for use in out-patient populations.

Cardiovascular effects of zimeldine

Sinus tachycardia is common after zimeldine overdosage, but major changes in blood pressure, conduction defects, prolonged repolarization and arrhythmias appear to be much less of a problem than with tricyclic antidepressants. At therapeutic dosage, there is no evidence of significant impairment of myocardial contractility or conduction with zimeldine. A fall in blood pressure was reported in one study, but not in others, and postural hypotension, though it may occur, is not common. These findings suggest that the use of zimeldine may be associated with a lower risk of cardiovascular toxicity than has been found with the tricyclic antidepressants.