fluvoxamine and hydroxymaprotilin

Antidepressants are ineffective in about 30% of patients with major depression. Some authors then advise treatment of non-responders with (non-tricyclic) more selective reuptake inhibitors. In a double-blind, partial crossover study, 71 patients were selected for treatment during 4 weeks with oxaprotiline and/or fluvoxamine, two non-tricyclic antidepressants that are selective reuptake inhibitors or noradrenaline and serotonin respectively. All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode. Only 13% of the patients responded, with 27% of them responding to oxaprotiline and none to fluvoxamine. Moreover, a low response of 27% was also obtained in the crossover phase, which included all non-responders to the first treatment, oxaprotiline being effective in 39% and fluvoxamine in 10% of the patients. The results indicate that selective reuptake inhibitors are not an effective alternative for non-responders to other cyclic antidepressants and that non-responders to "noradrenergic" antidepressants do not appear to have much chance of responding to "serotonergic" antidepressants and vice versa.

Topics: Adult; Anthracenes; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Oximes; Personality Disorders; Psychological Tests; Psychometrics

Antidepressants are ineffective in about 30% of the patients with major depression. Besides electroconvulsive therapy (ECT) and lithium, MAO inhibitors have been suggested as an alternative in such patients. In 2 controlled, partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants, the effect of the MAO inhibitor tranylcypromine was studied. The first study was an open comparison with L-5-hydroxytryptophan (L-5HTP), the second study a double-blind comparison with nomifensine. Neither the patients treated with L-5HTP nor the patients treated with nomifensine, except one, improved. In contrast, tranylcypromine was effective in 50% of the patients. The depressions of the responders to tranylcypromine appeared to be more endogenous (according Newcastle Scale II) and of shorter duration than those of the non-responders. It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants.

Topics: 5-Hydroxytryptophan; Adult; Aged; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Nomifensine; Oximes; Psychological Tests; Tranylcypromine

The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not.

Topics: Adult; Aged; Anthracenes; Antidepressive Agents; Depressive Disorder; Dexamethasone; Female; Fluvoxamine; Humans; Hydrocortisone; Male; Maprotiline; Middle Aged; Norepinephrine; Oximes; Prognosis; Psychiatric Status Rating Scales; Serotonin

L-5HTP and tranylcypromine were compared in an open, but controlled and cross-over study, in patients suffering from major depression; all were non-responders to several reuptake inhibitors, including oxaprotiline and fluvoxamine. After four unsuccessful sleep-deprivations, L-5HTP or tranylcypromine were given during four weeks in a crossover design. Of 17 patients given L-5HTP during both treatment periods, none responded, whereas of 26 patients treated with tranylcypromine, 15 responded. Thus, L-5HTP is not a therapeutically effective alternative in depressed patients who have not responded to reuptake inhibitors.

Topics: 5-Hydroxytryptophan; Adult; Aged; Carbidopa; Clinical Trials as Topic; Depressive Disorder; Drug Resistance; Drug Therapy, Combination; Fluvoxamine; Follow-Up Studies; Humans; Maprotiline; Middle Aged; Oximes; Random Allocation; Serotonin Antagonists; Stereoisomerism; Tranylcypromine

The autoinhibitory control of electrically evoked release of [3H]-dopamine and the properties of that induced by nicotinic receptor (nAChR) stimulation were studied in slices of the human neocortex. In both models [3H]-dopamine release was action potential-induced and exocytotic. The selective dopamine D2 receptor agonist (-)-quinpirole reduced electrically evoked release of [3H]-dopamine, yielding IC50 and I(max) values of 23 nM and 76%, respectively. Also, the effects of several other subtype-selective dopamine receptor ligands confirmed that the terminal dopamine autoreceptor belongs to the D2 subtype. The autoinhibitory feedback control was slightly operative under stimulation conditions of 90 pulses and 3 Hz, with a biophase concentration of endogenous dopamine of 3.6 nM, and was enhanced under blockade of dopamine reuptake. [3H]-dopamine release evoked in an identical manner in mouse neocortical slices was not inhibited by (-)-quinpirole, suggesting the absence of dopamine autoreceptors in this tissue and underlining an important species difference. Also, nAChR stimulation-induced release of [3H]-dopamine revealed a species difference: [3H]-dopamine release was evoked in human, but not in rat neocortical slices. The nAChRs inducing [3H]-dopamine release most probably belong to the alpha3/beta2subtype, according to the potencies and efficacies of subtype-selective nAChR ligands. Part of these receptors may be located on glutamatergic neurons.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adolescent; Adult; Aged; Alkaloids; Analysis of Variance; Animals; Autoreceptors; Azocines; Calcium; Child; Child, Preschool; Domperidone; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Feedback; Female; Fluvoxamine; Humans; In Vitro Techniques; Isoxazoles; Male; Maprotiline; Mice; Middle Aged; Neocortex; Nicotine; Nicotinic Antagonists; Potassium; Pyrrolidines; Quinolizines; Rats; Receptors, Nicotinic; Sulpiride; Time Factors; Tritium

The cardiovascular effect of cocaine in rabbits was examined for peripheral and central components and for the contribution of the primary actions of cocaine, i.e., inhibition of the high affinity uptake mechanisms for monoamines and local anesthesia. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), cocaine (0.2-5 mg kg-1) lowered the clearance of [3H]norepinephrine from plasma and increased the plasma norepinephrine concentration. Cocaine (0.2 and 1 mg kg-1) increased blood pressure and heart rate, whereas after 5 mg kg-1 heart rate and blood pressure decreased briefly and then recovered. In conscious rabbits, cocaine (0.2 and 1 mg kg-1) reduced renal sympathetic nerve activity and tended to reduce blood pressure and heart rate. Cocaine (5 mg kg-1) increased sympathetic nerve activity, blood pressure and the plasma norepinephrine and epinephrine concentrations. The effects of the lower doses were abolished in animals pretreated with oxaprotiline, but were not changed in animals pretreated with fluvoxamine or SCH 23390 (R-(+)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) + sulpiride. The effects of cocaine (5 mg kg-1) were attenuated by SCH 23390 + sulpiride but were not changed after oxaprotiline or fluvoxamine. Procaine (15 mg kg-1) mimicked the effects of cocaine (5 mg kg-1) on blood pressure and renal sympathetic nerve activity. Blood pressure also was increased by lidocaine (6 mg kg-1). It is concluded that cocaine enhances peripheral sympathetic neuro-effector transmission. In conscious rabbits, however, low doses fail to raise blood pressure because they simultaneously depress central sympathetic tone by blockade of the uptake of norepinephrine in the central nervous system. High cocaine doses cause sympathoexcitation in conscious rabbits. The mechanism seems to be dual: blockade of dopamine uptake in the central nervous system and a (peripheral or central) local anesthetic action.

Topics: Anesthetics, Local; Animals; Blood Pressure; Cocaine; Electric Stimulation; Fluvoxamine; Heart Rate; Lidocaine; Maprotiline; Procaine; Rabbits; Sympathetic Nervous System