R. Klysner

Characterization of human platelet beta-adrenoceptors

The widespread use of beta-adrenoceptor antagonists against hypertension, angina pectoris and migraine or as a preventive treatment after myocardial infarction has encouraged us to investigate the effects of these drugs on platelet function. The aim of this study was to examine whether beta-blocking drugs interfere with platelet beta- adrenoceptors and whether this dependency is related to their selectivity for beta-adrenoceptor subtypes. Beta-adrenoceptor stimulation of human platelets with isoprenaline increased cyclic AMP (cAMP), which is known to inhibit platelet aggregation. Furthermore, our studies showed that cAMP formation in vitro was stimulated by non-selective and beta 2-selective agonists, but not by the predominant beta 1-agonist prenalterol. Isoprenaline- stimulated cAMP formation was blocked by the non- selective beta-adrenoceptor antagonists propranolol, timolol, and alprenolol, while the beta 1-selective antagonists atenolol and metoprolol had no influence on an isoprenaline-induced cAMP formation. Receptor binding studies using (3H)-dihydroalprenolol revealed an IC50 value for propranolol of 85 nM, while metoprolol only displaced the bound (3H)-dihydroalprenolol at far higher concentrations (IC50, 20 microM). We conclude that the human platelet beta-adrenoceptors are mainly of the beta 2- subtype and that beta-adrenoceptor antagonists, especially the non-selective antagonists interfere with platelet function assessed as platelet cAMP formation.

Enhanced histamine- and β-adrenoceptor-mediated cyclic AMP formation in leukocytes from patients with endogenous depression

Beta-adrenoceptor-mediated cyclic AMP formation was found to be increased in leukocytes from manic-depressive patients during untreated depression when compared with euthymic patients treated with antidepressants. The difference was dependent on the stimulation used (isoprenaline or a combination of noradrenaline and phentolamine) and was only significant when the combination was used. Histamine-stimulated cyclic AMP formation in leukocytes was enhanced in patients with untreated depression, both when compared with euthymic patients suffering from manic-depressive illness, with or without treatment with antidepressant drugs, and also when compared with control persons without any known psychiatric disease. Although at variance with the results of some other studies on the same topic, the results of the present study indicate that changes in receptor function in leukocytes may be a state-dependent marker in depressive illness.

Antidepressants and components of the beta adrenoceptor system: studies on zimelidine

Treatment of rats with a number of antidepressants for one to several weeks leads to a decrease in the density of beta adrenoceptors in the cerebral cortex and other brain regions (Bergstrom and Kellar, 1979; Maggi et al., 1980). This reduction is accompanied by a concomitant decrease in the beta adrenoceptormediated cyclic AMP accumulation (Vetulani et al., 1976; Wolfe et al., 1978). Similar beta adrenoceptor alterations are also evoked by other antidepressant treatments. Thus, treatment with electro-convulsive therapy and monoamine oxidase inhibitors also induce beta adrenoceptor down-regulation (Gillespie et al., 1979; Sellinger-Barnette et al., 1980). The antidepressant treatments, however, have to be administered for a clinically relevant period of time before the changes are observable, whereas a single treatment does not change the number of beta adrenoceptors nor the associated cyclic AMP accumulation (Sarai et al., 1978; Vetulani et al., 1976; Wolfe et al., 1978).

Buspirone – a new non-benzodiazepine anxiolytic drug

Buspirone is an effective anxiolytic drug chemically and pharmacologically different from benzodiazepines. This drug has been reported to possess an anxiolytic effect comparable to that of benzodiazepines, while being less sedative, without psychomotor impairment and having no interaction with ethanol. The neurochemical effects of buspirone are quite different from those of benzodiazepines, indicating an important role for monoamines in anxiolysis. Together with a short review of the literature on buspirone, a few of our preliminary results concerning long-term buspirone administration on catecholamine transmission are mentioned.

Agonist og antagonist binding til beta-adrenerge receptorer efter antidepressiv behandling

Langtidsbehandling rned en raekke antidepressiva medforer reduktion i antallet af beta-adrenerge receptorer i rottehjerne, en aendring, der soges relateret til antidep-ressivas terapeutiske effekt. Imidlertid er det ved behandling med flere af de nyere antidepressiva fundet, at kun funktionen af receptoren nedsaettes, medens antallet af beta-receptorer tilsyneladende er uaendret.Denne diskrepans diskuteres, specielt med hensyn til forskelle i agonist og antagonist binding til beta-receptoren efter antidepressiv behandling.

Beta-adrenerg receptorfunktion ved depression og under antidepressiv behandling

Rene Klysner, kandidatstipendiat ved Farmakologisk Institut, Kobenhavns Universitet, arbejder med eksperimentel psykofarmakologi, isaer vedrorende antidepressivas kroniske virkninger pa adrenerge receptorer.Arne Geisler, speciallxge i psykiatri, har siden 1973 som lektor ved Farmakologisk Institut, Kobenhavns Universitet arbejdet med eksperimentel psykofarmakologi.Raben Rosenberg, lektor ved Psykokemisk Institut, Kobenhavns Universitet, har forsket indenfor biologisk psykiatri, specielt omkring aminosyretransport over biologiske membraner samt udforskning af mulige biologiske markorer ved affektive tilstande.I artiklen gives der en kort redegorelse for baggrunden for undersogelser vedrorende beta-adrenerge receptorer og cyklisk AMP dannelse i blodceller fra manio-drepressive patienter. Forelobige resultater fra en undersogelse omfattende alfa- og beta-adrenerg samt histaminstimuleret cyklisk AMP dannelse i trombocytter og leukocytter hos 71 manio-depressive patienter og raske kontrolpersoner praesenteres. P...