fluvoxamine and clovoxamine

Platelet 5-HT levels and scores on the 17-item Hamilton Rating Scale for Depression (HRS) were studied in patients with unipolar depression before and after antidepressant treatment. Before treatment there were no differences in platelet 5-HT values or in HRS scores between patients who showed a good and a poor therapeutic response. Repeated administration of 5-HT uptake inhibitors (amitriptyline, clovoxamine, fluvoxamine) for 28 days markedly decreased platelet 5-HT levels. Chronic treatment with trazodone or maprotiline (weak inhibitors of platelet 5-HT uptake) produced no changes in platelet 5-HT levels. No significant correlation was observed between platelet 5-HT concentrations and the HRS scores before or during treatment. The findings suggest that the changes in platelet 5-HT levels after antidepressant treatment are mainly due to the effects of antidepressants on the 5-HT uptake system.

Topics: Adult; Aged; Amitriptyline; Antidepressive Agents; Blood Platelets; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Oximes; Psychiatric Status Rating Scales; Serotonin; Trazodone

The influence of 17 days of administration of fluvoxamine or clovoxamine, two new antidepressant agents, on the kinetics of a single intravenous dose of digoxin, and on self-rated parameters of sedation, mood, and sleep, was evaluated in a series of healthy volunteers. In the fluvoxamine study, subjects received fluvoxamine, 100 mg daily, or matching placebo for 17 consecutive days in a crossover design. For the clovoxamine study, subjects received clovoxamine, 150 mg daily, or placebo for 17 days. All treatments were double blind. At the end of each treatment, digoxin kinetics were evaluated following a single 1.25 mg intravenous dose. Compared to the placebo condition, fluvoxamine had no significant influence on digoxin elimination half-life (57 vs 47 hours), volume of distribution (10.5 vs 10.3 liters/kg), total clearance (2.4 vs 3.0 ml/min/kg), or 72 hour urinary excretion (33 vs 37 percent of the dose). Likewise clovoxamine did not alter digoxin elimination half-life (39 vs 40 hours), volume of distribution (10.7 vs 10.2 liters/kg), or total clearance 3.4 vs 3.4 ml/min/kg). 72 hour urinary excretion of digoxin was slightly increased by clovoxamine (41 vs 50 percent of the dose, P less than .05). Self-ratings indicated a sedating effect of fluvoxamine, with reports of difficulty attaining morning alertness. These effects were not reported with clovoxamine. Thus clovoxamine and fluvoxamine appear to have differential effects on sleep and alertness in healthy volunteers. However, neither have an important influence on the kinetics of digoxin.

Topics: Adult; Antidepressive Agents; Arousal; Creatinine; Digoxin; Double-Blind Method; Fluvoxamine; Half-Life; Humans; Male; Oximes; Random Allocation; Sleep

1 Fluvoxamine and clovoxamine, two new potential antidepressants were given to 27 healthy male volunteers in a double-blind, placebo controlled, three-way crossover study. 2 Neither compound affected the electrical intervals of 24 h ambulant electrocardiographic monitoring with the exception of a small increase in R-R interval. 3 There were no changes in blood pressure measurements. 4 The only notable unwanted symptom was nausea for both fluvoxamine and clovoxamine.

Topics: Antidepressive Agents; Blood Pressure; Fluvoxamine; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Oximes; Placebos; Time Factors

In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxami

Topics: Adult; Antidepressive Agents; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Ethers; Female; Fluvoxamine; Humans; Kinetics; Male; Oximes; Placebos; Psychometrics

A normal-phase column liquid chromatographic assay for fluvoxamine, a recently introduced atypical antidepressant, has been developed. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane. These extracts were then injected into a 5-microns Resolve spherical silica column. Fluvoxamine and the internal standard, clovoxamine, were detected at a wavelength of 254 nm. Standard curves were linear over the concentration range 2-400 ng/ml. Acceptable coefficients of variation were obtained for both within-run and day-to-day studies. The estimated limit of detection is 0.5 ng/ml, and selected drugs checked for coadministration show no analytical interference. This assay was used to evaluate the pharmacokinetics of fluvoxamine in rats.

Topics: Animals; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Fluvoxamine; Humans; Indicators and Reagents; Oximes; Rats; Reference Standards; Spectrophotometry, Ultraviolet

Topics: Antidepressive Agents; Chromatography, High Pressure Liquid; Fluvoxamine; Humans; Oximes; Spectrophotometry, Ultraviolet

Topics: Antidepressive Agents; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Fluvoxamine; Humans; Liver Cirrhosis; Oximes; Spectrometry, Fluorescence

Freely moving rats were implanted with cortical, caudal, thalamic, and reticular electrodes. Drugs were infused intravenously at a constant rate up to a final cumulative dose of 40, 50, or 60 mg/kg. Doses of 10 mg/kg imipramine, viloxazine, desmethylimipramine, mianserin, and maprotiline produced spike-wave complexes, spikes, and increased spindling. General sustained discharges occurred after 20 mg/kg of mianserin, viloxazine, imipramine, desmethylimipramine and amitriptyline, and after 30 mg/kg of maprotiline. An abnormal high-amplitude pattern was evident after mianserin, amitriptyline, imipramine, and desmethylimipramine. On the average, seizures were observed at 40 mg/kg and were seen after desmethylimipramine (50 mg/kg), mianserin (30 mg/kg), amitriptyline (20 mg/kg), imipramine (40 mg/kg), maprotiline (40 mg/kg), and zimelidine (50 mg/kg). Ranking the tested antidepressants in decreasing order in accordance with their relative (pro)convulsive properties gives: amitriptyline greater than mianserin much greater than imipramine greater than desmethylimipramine greater than viloxazine much greater than maprotiline much greater than zimelidine greater than clovoxamine greater than nomifensine = fluvoxamine.

Topics: Amitriptyline; Animals; Antidepressive Agents; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Fluvoxamine; Imipramine; Male; Maprotiline; Mianserin; Oximes; Rats; Rats, Inbred Strains; Seizures; Viloxazine

Reserpine + nialamid administration to the rat induces a strong yellow fluorescence of the neuronal bodies of the raphe, due to serotonin (5-HT) accumulation. Under these conditions, administration of clomipramine (an antidepressant drug acting preferentially on 5-HT-mediated neurons) induces a decrease of intraneuronal fluorescence and its interneuronal diffusion. On this pattern we administered new antidepressant drugs which act on 5-HT neurons in a much more intensive way than clomipramine (fluvoxamine, clovoxamine, LM 5008, citalopram, Ro 11-2465). To varying degrees, we observed in the raphe, in addition to a decrease in intraneuronal fluorescence and interneuronal diffusion, the presence of a yellow fluorescence in capillary walls. It seems that under these antidepressants, 5-HT, which is outside neuronal bodies because of uptake blockade, is partly caught by the capillary walls. In these walls rich in monoamine oxydase, 5-HT would be catabolized, 5HIAA dispersed in the blood and thus, this 'capillary effect' could correspond to a loss of 5-HT in the raphe. Antidepressant drugs preferentially acting upon noradrenaline (NA) neurons do not, in this model, induce analogous phenomena in NA cell bodies of the locus coeruleus. So the 'capillary effect' differentiates antidepressant drugs acting specifically on 5-HT or NA neurons. It may be considered together with other parameters which also indicate asymmetries on the modes of action of antidepressant drugs, such as effects on monoamine turnover (increase for NA and decrease for 5-HT) and on receptor sensitivity (decrease for NA and increase for 5-HT).

Topics: Animals; Antidepressive Agents, Tricyclic; Benzofurans; Brain Stem; Citalopram; Clomipramine; Ethers; Fluvoxamine; Imipramine; Indoles; Locus Coeruleus; Male; Microscopy, Fluorescence; Norepinephrine; Oximes; Piperidines; Propylamines; Raphe Nuclei; Rats; Receptors, Serotonin; Serotonin

A high-performance liquid chromatographic system for the direct determination of the antidepressants clovoxamine and fluvoxamine in plasma is described. The primary amines are derivatized with the fluorogenic reagent fluorescamine in order to increase the sensitivity and selectivity, but also to decrease the polarity of the amines. The band broadening of some combinations of pre-column and analytical column is compared for the fluorescamine derivative of fluvoxamine. The combination of a pre-column containing RP-2 and an analytical column containing RP-8 has been successfully used for the determination of the two antidepressants in plasma. At relatively low concentrations of the drugs, a simple step-gradient elution is required for the removal of a large proportion of the more polar components of the samples. Concentrations in the range of 10-1000 ng clovoxamine per ml plasma were determined by means of external standardization and show a good correlation with the data of a more laborious gas chromatographic method. The detection limits for clovoxamine and fluvoxamine are approximately 3 ng/ml in plasma.

Topics: Antidepressive Agents; Chromatography, High Pressure Liquid; Ethers; Fluorescamine; Fluvoxamine; Humans; Mathematics; Oximes