Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers

Abstract To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin w…

Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial.

Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psych…

Abstract of the 68th Meeting (Spring Meeting) 6–9 March 1990, Heidelberg

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…

Spatial learning and expression patterns of PP1 mRNA in mouse hippocampus.

<i>Background:</i> Synaptic plasticity is believed to be the major cellular basis for learning and memory. Protein phosphorylation is a key process involved in changes in the efficacy of neurotransmission. In long-term changes synaptic plasticity is followed by structural plasticity and protein de novo synthesis. Such mechanisms are believed to build the basis of hippocampal learning and memory investigated in the Morris water maze (MWM) task. To examine the role of dephosphorylation during that model for spatial learning, we analyzed protein phosphatase 1 (PP1) expression in the hippocampus of mice at various stages of the task and in two groups with different learning abilitie…

The neuroendocrinological profile of roxindole, a dopamine autoreceptor agonist, in schizophrenic patients

Roxindole is a potent autoreceptor-selective dopamine agonist with additional properties as a serotonin reuptake inhibitor and 5-HT1A agonist. In order to get more insight into its mode of action in various psychiatric populations, we evaluated the effects of subchronic roxindole treatment on pituitary and adrenal hormone secretion, i.e. release of prolactin, thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and cortisol. Fifteen schizophrenic patients with positive and negative symptomatology, respectively, were treated with roxindole for 28 days. Both basal and thyrotropin releasing hormone (TRH) -induced prolactin secretion diminished significantly to 26.4…

Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion

Zopiclone is a new short half-life cyclopyrrolone hypnotic agent acting at the GABA-benzodiazepine receptor complex. In order to characterize its pharmacological profile, the effects of 7.5 mg zopiclone on nocturnal melatonin secretion were investigated under polysomnographic control in 11 healthy subjects following acute and subchronic administration as well as after abrupt discontinuation of the drug. No effect of zopiclone on the melatonin plasma levels could be observed. Regarding both total melatonin production and the temporal pattern of melatonin secretion during the night, there was no difference between placebo baseline condition, acute and subchronic administration, and discontinu…

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…

Automated Determination of Fluvoxamine in Plasma by Column-Switching High-Performance Liquid Chromatography

Abstract A column-switching system with high-performance liquid-chromatographic separation and ultraviolet detection is described for automated determination of fluvoxamine in human plasma or serum. Samples were injected and the drug was retained in a clean-up column [20 x 4.6 mm (i.d.)] filled with C8 reversed-phase material (10-micron particles). After unwanted material was washed out, the drug was eluted and separated with an analytical chromatography column, 4.6 x 250 mm (i.d.), filled with Nucleosil 100 CN (5-micron particles) with an acetonitrile:methanol:0.01 mol/L phosphate buffer eluent (188:578:235 by vol) at a flow rate of 1.5 mL/min for < 20 min and detected by spectromet…

Effects of ovariectomy and steroid replacement on GABAA receptor binding in female rat brain.

Abstract The specific binding of tritiated muscimol to γ-aminobutyric acid (GABA) receptor sites was studied in distinct brain areas of female rats during different endocrine states. In diestrous rats with intact ovaries the highest receptor densities were found in the cortex (10.24 pmol/mg protein) and the lowest concentrations in the mediobasal hypothalamus (3.29 pmol/mg protein). Four weeks after removal of the ovaries, the number of binding sites was enhanced up to 2.4-fold in all brain areas investigated: the preoptic brain area, mediobasal hypothalamus, corticomedial amygdala, and cerebral cortex. The affinity of the binding sites remained unchanged. Substitution of estradiol and prog…

IBZM-SPECT bei Neuroleptikatherapie

Mit IBZM — einem mit Jod-123 markierten Benzamid — ist es erstmalig moglich, die Dopamin-D2-Rezeptoren mit der Single-Photonen-Emissions-Computertomographie (SPECT) darzustellen. Das trotz der fehlenden ab-soluten Quantifizierung mit SPECT diese Methode hilfreich sein kann fur die Messung der D2-Rezeptoren, wurde schon von der Arbeitsgruppe von Brucke [1] dargestellt. Gegenstand unserer eigenen Studien war die Untersuchung der D2-Rezeptorbesetzung (RB) unter Haloperidol, Benperidol und Clozapin im Zusammenhang mit klinischen Daten und Prolaktinspiegeln.

Benzodiazepinrezeptorbindung im [123I]-IOMAZENIL-SPECT in Relation zu Cortisol-Plasmaspiegeln

Mit Iomazenil, dem mit 123Iod markierten Benzodiazepinantagonisten, und der Single Photonen Emissions Tomographie (SPECT) ist die in vivo-Darstellung von Benzodiazepinrezeptoren (BZR) moglich. Wir fanden in fruheren Untersuchungen eine signifikante Verminderung der lomazenil-Bindung bei Panikpatienten im Vergleich zu Patienten mit Depressionen (Schlegel et al. 1994). Zwischen dem GABA/BZR-System und Cortisol sind vielfaltige und komplexe Wirkzusammenhange beschrieben worden (De Souza et al. 1990). Nach Adrenalektomie wurde bei Ratten eine Zunahme der BZR-Dichte beschrieben (Miller et al. 1988, Acuna et al. 1990). Diese Effekte waren nach Corticosteroidgabe reversibel. Wahrend sich der Effek…

Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT

By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminer…

Standardisierte Verlaufsdokumentation als Grundlage zur Verbesserung der Prozessqualit�t der station�ren psychiatrischen Behandlung

Es wird eine standardisierte Verlaufsdokumentation zur detaillierten Beschreibung und Analyse des Behandlungsprozesses fur stationare psychiatrische Patienten vorgestellt. Im Rahmen eines an der Psychiatrischen Klinik der Universitat Mainz durchgefuhrten Pilotprojekts, zunachst beschrankt auf Patienten mit einem depressiven Syndrom, wurde der mit Hilfe wochentlich durchgefuhrter psychopathologischer Ratings erfasste klinische Zustand zusammen mit den therapeutischen Masnahmen fur die einzelnen Patienten im Zeitverlauf abgebildet. Es hat sich gezeigt, dass die Visualisierung des Behandlungsprozesses die klinische Arbeit unterstutzen und die Anwendung von Therapiestandards bei klinischen Ents…

Interleukin-6 in plasma collected with an indwelling cannula reflects local, not systemic, concentrations.

[123I]IBZM SPECT in patients treated with typical and atypical neuroleptics: relationship to drug plasma levels and extrapyramidal side effects

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly di…

Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is a physiologically relevant modulator of GABA-ergic neurotransmission.

Abstract 3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of 3 H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of 3 H-muscimol to GABA A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5…