0000000000148477
AUTHOR
E. Hammes
Roxindole, a dopamine autoreceptor agonist, in the treatment of major depression
Roxindole is a potent autoreceptor-“selective” dopamine agonist originally developed for the treatment of schizophrenic syndromes. The drug also inhibits 5-HT uptake and has 5-HT1A agonistic actions. In this open clinical trial 12 in-patients suffering from a major depressive episode (DSM-III-R) were treated with roxindole for 28 days in a fixed dosage of 15 mg per day. A reduction of at least 50% in HAMD-17 total scores was observed in 8 out of 12 patients after 4 weeks (mean HAMD-17 reduction of 56% in all patients), while 4 patients did not respond to roxindole treatment. Half of the patients showed a complete psychopathological remission (HAMD-17 <8). Roxindole's onset of antidepressant…
Sub-acute effects of interferon-α2 on adrenocorticotrophic hormone, cortisol, growth hormone and prolactin in humans
Abstract This study investigated the chronic effects of interferon-α2 (IFN-α2) on hormonal secretion in humans. Six patients suffering from chronic hepatitis B or C infection received SC doses of 3 million IU IFN-α2 three times a week for 4 mo. Each patientwas examined for hormone secretion four times: the day before initial IFN-α2 administration (day 0), the day of the first injection (day 1), and 4 wk after start of IFN therapy on days 27 (without IFN administration) and 28 (with IFN administration). Adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (hGH), and prolactin (PRL) were measured in plasma samples drawn at 30-min intervals between 1600h and 2400h. Acute administratio…
Circadian variations in antigen-specific proliferation of human T lymphocytes and correlation to cortisol production.
Cortisol is a well-known immunosuppressant when used therapeutically. The present investigation was set out to study if diurnal variations in endogenous cortisol production are reflected by changes in proliferative responses of human lymphocytes to either a mitogen (phytohemagglutinin-A, PHA) or an antigen (tetanus toxoid, TT) stimulus. The study included eight healthy volunteers. Blood was withdrawn at 0200, 0600, 1000, and 1800h for preparation of lymphocytes and determination of cortisol in plasma. Isolated cells were incubated without (baseline activity) or with inclusion of either 1 micrograms PHA or 10 micrograms TT. Proliferation was measured by labelling with 3H-thymidine for 16 h o…
Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients.
Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before com…
Nonlinear pharmacokinetics of fluvoxamine and gender differences.
This prospective study assessed fluvoxamine serum concentrations under two different fixed doses. The study included 15 male and female patients who met the DSM-III-R criteria for major depression. They were prescribed 50 mg fluvoxamine twice a day for 2 weeks and 100 mg twice a day thereafter. Drug monitoring was carried out on days 14 and 28. Fluvoxamine serum concentrations were highly variable between patients. After the dose was doubled, the serum concentrations of fluvoxamine increased disproportionately (mean, 3.4-fold), and there was a significantly (p < 0.05) more pronounced increase in men (4.6-fold) than in women (2.4-fold). These results provide evidence of nonlinear, sex-depend…
Interferon-Alpha-2-Induced Stimulation of ACTH and Cortisol Secretion in Man
Short-term effects of interferon-alpha 2 on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol were measured in man in relation to interferon absorption. Interferon-alpha 2 was given subcutaneously at a dose of 3 x 10(6) IU at 17.00 h to 2 female and 5 male patients who suffered from chronic hepatitis B infection and who had not previously been treated with interferon. Plasma levels of ACTH, cortisol and interferon-alpha were determined at 30-min intervals between 16.00 and 24.00 h. In each patient a similar cortisol, ACTH and interferon-alpha profile was determined on a day, when no interferon-alpha treatment was given. Interferon-alpha plasma levels peaked around 21…