RESUMEN

Humoral mechanism should be responsible for activation of PNMT (phenylethanolamine N-methyltransferase) by CRF (corticotropin-releasing factor) in vivo (Lima and Sourkes, 1987). Small amounts of serum (10 microliters) caused a sig. dose dependent activation of bovine PNMT activity (19.0 +/- 1.8%) changing in Km and Vmax values in vitro. Human/rat or ovine CRF--in high amounts (8.4 nmol) only--increase at the rate of just 10% bovine PNMT activity in vitro. At the moment, we do not know which factor in serum is responsible for the increase in A (adrenalin) synthesis in vitro.

Asunto(s)

Asunto(s)

RESUMEN

15 depressive patients and 15 controls, 9 of them age- and sex-matched, were administered 0.2 mg/70 kg i.v. fentanyl, a specific and highly potent mu-opiate receptor agonist. Growth hormone response was significantly reduced in depressive patients in comparison to controls, whereas prolactin response did not significantly differ between the two groups. Cortisol plasma concentration increased in depressive patients and decreased in controls. The difference between the groups failed to reach statistical significance. Only in patients, but not in controls, fentanyl led to a significant increase in plasma noradrenaline. In contrast, a significant increase in the visual analogue scale for the evaluation of psychotropic drug effects was found only in controls after fentanyl administration. From these preliminary results in connection with other studies we conclude a possible involvement of a disturbed opioid system at least in a subgroup of depressive patients.

Asunto(s)

Asunto(s)

RESUMEN

The growth hormone (GH) response to clonidine (CLON) has been investigated to date mostly with CLON doses of 2.0 micrograms/kg or 150 micrograms intravenously (IV). The present study investigated GH and blood pressure (BP) responses to CLON (2.0 and 1.5 micrograms/kg IV) (Study I). Twelve healthy male volunteers were tested with the two CLON doses and saline in a cross-randomized design. Plasma GH, noradrenaline (NA) and cortisol concentrations, BP and sedation were determined. CLON (1.5 and 2.0 micrograms/kg) induced a significant dose-dependent GH increase, but only the 2.0 micrograms/kg dose differentiated GH responders from nonresponders. In contrast to GH, NA, cortisol, and BP did not differ significantly after either CLON dose. We also studied GH responses to repeated CLON stimulation (Study II). Ten healthy male volunteers were given four CLON tests (2.0 micrograms/kg) at three-week intervals. The nine volunteers who participated in both studies were investigated over a time course up to 21 months. The subjects could be classified into those who showed consistent GH responses greater than 5 ng/ml, those who showed consistent GH responses less than 5 ng/ml, and those who showed both degrees of responses.

Asunto(s)

Asunto(s)

RESUMEN

The influence of the histaminergic system on fentanyl (Fe)-induced growth hormone (GH) and prolactin (PRL) release as well as on Fe-induced increase of noradrenaline (NA) plasma levels has been studied in male volunteers. These volunteers received, according to a randomized block design, different pretreatments: the H1-antagonist dimethindene (Di) (0.1 mg/kg i.v.), or the H2-antagonist cimetidine (Ci)(5 mg/kg i.v.), or a combination of dimethindene and cimetidine (Di + Ci), or saline. The PRL increase caused by Fe (0.2 mg/70 kg) was not altered by pretreatment with the H1-antagonist Di, the H2-antagonist Ci, or the combination of both. The increase of NA plasma levels after Fe also was not modified by the histamine antagonists. In contrast, the maximum GH increase after Fe was blunted by the combination of Ci and Di, but not by either Ci or Di alone. These results suggest an involvement of the histaminergic system in opiate-induced GH-release.

Asunto(s)

RESUMEN

The therapy of depressions with amine precursors is based on the hypothesis of an amine deficiency in depression. A brief review of different trials with these substances is given. However, the therapeutic effects achieved were not satisfactory, although treatment with 5-HT or with amine precursors combined with lithium or MAO-inhibitors seemed to be more successful. Furthermore, the difficulties in interpreting these somewhat disappointing results is pointed out.

Asunto(s)

Asunto(s)

RESUMEN

Several neuroendocrine studies with the clonidine-growth hormone stimulation test show endogenous depressive patients to have a reduced GH response as compared to neurotic depressives, schizophrenics and controls. The blunted GH response to clonidine seems to be a trait marker or vulnerability factor for mono- and bipolar endogenous depression. It could be explained by a reduced postsynaptic alpha 2-adrenoceptor sensitivity or of structures related to them. The sensitivity of alpha 2-adrenoceptors is influenced by both, the endorphinergic and cholinergic systems. First results supporting this concept are presented and discussed.

Asunto(s)

Asunto(s)

RESUMEN

The effect of Fentanyl (FE), an opioid agonist, on neurosecretion and mood was investigated in normal volunteers using doses of 0.1, 0.2, 0.25 mg/70 kg. FE caused a strong dose-dependent increase in prolactin (PRL) secretion in every subject. In contrast, growth hormone (GH) was stimulated significantly at the highest dose only. Additionally, FE induced a significant increase in feeling of wellbeing measured by the Visual Analogue Scale (VAS).

Asunto(s)

Asunto(s)

RESUMEN

The dependence of the growth hormone (GH) response to clonidine (CLON) on alcohol drinking habits and on the menstrual cycle was investigated. GH response to CLON (0.15 mg i.v.) was blunted in 6 of 9 male, regularly beer-drinking non-depressed probands. After 14-17 and 30-37 days of abstinency, the probands showed a slight but not significant increase of the CLON stimulated GH maxima, and with great variability. During their menses, female probands had a significantly lower GH response to CLON than during ovulation. For these reasons, both alcohol drinking habits and, in females, the day of the menstrual cycle should be considered when the CLON-GH test is carried out in clinical studies.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

The discovery of the anti-depressive effects of imipramine and the MAO inhibitors, associated with the occasional depressions occurring during reserpine treatment was the starting point of modern research into depression. The concern with the neurochemical actions of these substances led to putting forth the noradrenaline and serotonin hypothesis of depression in the mid-60s. According to this, there is supposed to be a deficiency of noradrenaline and/or serotonin at the nerve endings in depression. This amine deficiency hypothesis has not been proved as yet in spite of intensive neurobiological research. Clinical as well as animal experiments in depressive patients with antidepressive drugs have led to the assumption that, in "endogenous" depression particularly, but also for the antidepressive mechanisms, alpha- and beta-adrenergic receptor changes play an important part.

Asunto(s)

RESUMEN

We interpreted our previous findings obtained with clonidine in depressive patients to indicate that in endogenous depressive patients--in contrast to neurotic depressive patients and controls--there is a reduced sensitivity of postsynaptic alpha-adrenergic receptors or of structures related to them. In the present study, after desipramine (DMI) (75 mg i.m.), endogenous depressives show a significantly reduced growth hormone (HGH) response as compared to neurotic depressive patients and to controls. The HGH response to DMI can be blocked by pretreatment with the alpha-blocker phentolamine (30 and 60 mg i.v.). Therefore we assume that in the DMI test, postsynaptic alpha-receptors are involved, thus giving further evidence for the importance of postsynaptic alpha-receptors in depression.

Asunto(s)

Asunto(s)