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At least 37 records · Page 2Linked to original sources
PubMed2002

Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents.

This study characterized the influence of acute administration of diverse classes of antidepressant agent upon the spontaneous locomotor activity (LA) of mice in a novel, open-field environment. The selective serotonin (5-HT) reuptake inhibitors (SSRIs), citalopram, fluoxetine, paroxetine, fluvoxamine, litoxetine and zimelidine, dose-dependently enhanced LA. Their actions were mimicked by the mixed 5-HT/noradrenaline (NA) reuptake inhibitors (SNRIs), venlafaxine, duloxetine and S33005. In contrast, clomipramine only slightly elevated LA and two further tricyclics, imipramine and amitriptyline, were inactive. Further, the selective NA vs. 5-HT reuptake inhibitors (NARIs), reboxetine, desipramine, maprotiline, nisoxetine and nortriptyline all failed to increase LA. The "atypical antidepressants," mianserin and mirtazapine, neither of which modify 5-HT reuptake, as well as the mixed SSRI/5-HT(2) antagonists, nefazodone and trazodone, also failed to increase LA. Doses of SSRI and SNRI which increased LA did not modify motor performance in the rotarod test. Further, they did not enhance LA in rats, suggesting that this response is characteristic of mice. Finally, upon prehabituation of mice to the activity chamber, the SSRI, citalopram, and the SNRI, venlafaxine, failed to increase LA. In conclusion, in mice exposed to a novel environment, inhibition of 5-HT reuptake by SSRIs and SNRIs enhances spontaneous LA in the absence of a generalized influence upon motor function. This response provides a simple parameter for characterization of SSRIs and SNRIs, and differentiates them from other classes of antidepressant agent. Although an influence upon arousal and/or anxiety is likely related to the increase in LA, the functional significance of this response requires additional elucidation.

Adrenergic Uptake Inhibitors↗
PubMed2000

[Antidepressive agents in dementia].

Antidepressants are used in demented patients for treating depressive symptoms as well as other non-cognitive symptoms including agitation, aggression and irritability. As patients are usually elderly, a dose adjustment is mandatory for all classes of antidepressants. New antidepressants such as the SSRIs and the reversible MAO inhibitors should be the first-line agents in these patients, because their efficacy is not different from that of classic TCA, but they have advantages regarding frequency of adverse effects, ease of use and safety. Improvement in cognitive performance, however, may not be expected from the new antidepressants. For the treatment of agitation, aggression and irritability, antipychotics and benzodiazepines are in frequent use, although their adverse effects are particularly problematic in demented patients. Good alternatives are the antidepressant trazodone and citalopram. All medications mentioned have been studied on small patient samples, so treatment recommendations must be given cautiously.

Aged↗
PubMed1976

[Contribution to the effect of tri and tetracyclic antidepressive agents on the heart and blood circulation].

In 47 patients ECG tracings were recorded and cardiovascular values determined before therapy, during treatment with antidepressive agents after it had been in progress for at least 3 weeks, and 4 weeks after withdrawal of therapy. In a further 19 patients in whom antidepressive therapy could not be withdrawn, the same test battery was repeated after an average period of 13 months. No serious disturbances of cardiac rhythm were detected and certain changes in ECG criteria (prolongation of PR interval, widening of QRS complex, prolongation of QTc time and T-wave flattening) proved to be reversible. There was no difference between tricyclic and tetracyclic antidepressive agents. We are nevertheless of the opinion that ECG and cardiac function should be carefully monitored in elderly patients and in those on prolonged therapy with high doses of antidepressives. The results of this study are discussed and compared with previously published findings.

Adolescent↗
PubMed1979

Metabolic fate of 3-(3-methylphenyl)-5-hydroxymethyl-2-oxazolidinone (toloxatone), a new antidepressant agent, in man.

1. In man, the antidepressant agent 3-(3-methylphenyl)-5-hydroxymethyl-2-oxazolidinone (toloxatone) on oral dosing was mainly eliminated in urine (80% dose in 12 h). 2. Plasma concn. of total radioactivity was max (5.8 micrograms equiv./ml) at 30 min to 1 h after administration and declined rapidly (t1/2, 1.25 h). Unchanged drug accounted for 48, 32 and 13% of plasma radioactivity at 15 min, 1 h and 6 h, respectively. 3. The drug was extensively metabolized. The major urinary metabolites were 3-(3-carboxyphenyl)-5-hydroxymethyl-2-oxazolidinone and a glucuronide of toloxatone. A minor urinary metabolite, characterized as a phenolic derivative, was also excreted conjugated.

Adult↗
PubMed2005

Potential effects of antidepressant agents on the growth and development of children and adolescents.

The regulatory bodies of both the United States and United Kingdom have issued cautionary statements about prescribing antidepressant medications to treat major depressive disorder (MDD) in children younger than age 18. Despite these cautions, antidepressant agents, particularly SSRIs and serotonin activators, are regularly used to treat MDD in this age group, and increasingly so in very young children. This article considers the possible effects of antidepressant agents on the growth and development of children younger than age 18 and provides recommendations for the use and careful monitoring of these medications, including screening for physiological effects, selfinjurious behavior, and suicidal ideation. Guidelines for use of antidepressant agents with these populations include incorporating medications into comprehensive, holistic treatment, assessing for onset of severe akathesia as a marker of increased risk for self-harm, and advocating for more clinical trials of these medications in different childhood age groupings.

Adolescent↗
PubMed1978

Effects of antidepressant agents on the synthesis of brain monoamines.

The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents.

5-Hydroxytryptophan↗
PubMed1981

Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects.

The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.

Administration, Oral↗
PubMed2001

[Current drug treatment. Effects of antidepressive agents in nervous and stress-related disorders].

Antidepressants have a much broader range of indication than the name suggests. The efficacy of antidepressant treatment of nervous and stress-related disorders has been documented in several controlled trials, both in comparison with placebo and with other antidepressants. Most studies have included testing in panic disorder, with or without agoraphobia, and obsessive compulsive disorder, but there is empirical evidence for the efficacy of the drugs in most anxiety disorders. Antidepressants with a preference for serotonergic neurotransmission (i.e. clomipramine and SSRIs (serotonin specific reuptake inhibitors) are particularly effective in the treatment of panic disorder and obsessive compulsive disorder. Owing to their more favourable side effect profile as compared with classical antidepressants, the SSRIs are considered to be the drugs of first choice, except for generalised anxiety disorder, where the efficacy of venlafaxine has been most thoroughly documented. Studies comparing different antidepressant are warranted. So are studies elucidating the relative benefits of drug treatment and psychotherapy, but, with the concept of modern anxiety treatment, there is no principal objection to combining the two treatment methods.

Agoraphobia↗
PubMedDate not supplied

[The role of serotonergic system in the mechanism of action of antidepressant agents].

Thirty eight years after the successful clinical introduction of antidepressant agents, there has been an important progress in the knowledge and changes in thinking about the role of central serotonergic system in depression and in the mechanism of their therapeutic efficacy. Although it is not clear whether an increase or decrease in serotoninergic function is more important in antidepressant action of agents, there is increasing evidence that almost all antidepressant drugs can induce changes in the sensitivity of somotodendritic 5-HT1A autoreceptors and postsynaptic 5-HT2 receptors in spite of very different pharmacological profiles after a single administration. The question arises as to the causal nature of the relationship between these effects and beneficial clinical action. Further studies are still required to dispel these doubts.

Antidepressive Agents, Tricyclic↗
PubMed1983

Q-T prolongation and torsades de pointes ventricular tachycardia produced by the tetracyclic antidepressant agent maprotiline.

Tricyclic antidepressant drugs such as imipramine and desipramine have long been known to produce cardiovascular side effects including sinus tachycardia, prolongation of the P-R, QRS, and Q-T intervals, and decreased T-wave amplitude. Life-threatening ventricular ectopic activity has occurred after tricyclic drug overdose. Recently, maprotiline (Ludiomil), a tetracyclic anthracene-derivative antidepressant, has become available for the treatment of affective disorders. It appears as effective as the tricyclic drugs in relieving unipolar depression. Although several studies have reported a low incidence of cardiovascular side effects, others show little difference between the tetracyclic and tricyclic drugs. This report describes a patient in whom maprotiline treatment caused Q-T prolongation and life-threatening torsades de pointes ventricular tachycardia (VT).

Aged↗