Effect of fluacizine on the uptake of exogenous noradrenalin.
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Biomedical subjects
Publications and source records attributed to V A Arefolov.
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Spectrofluorometry, fluorescent histochemistry and cytochemical electron microscopy were employed in studying the capacity of the neuroleptics trifluoroperazine, chlorpromazine and droperidol to bar the capture and accumulation of exogenous norepinephrine (NE) in the tissue, of adrenergic nerve fibers and synaptic vessels of an isolated Vas deferens of the rat. Trifluoroperazine and droperidol were found to be devoid of the property to inhibit the capture and accumulation of NE in the tissue, nerve fibers and in the synaptic vesicles. Chlorpromazine blocked the accumulation of the neurotransmitter, when the mediator was added in a concentration of 1 gamma/ml and failed to produce an inhibitory effect, when NE was used in a greated concentration (30 gamma/ml). It is concluded that all the studied neuroleptics do not hinder the neurotransmitter gaining access into synaptic vesicles, when it is accumulated in the axoplasma.
The morphofunctional state of different links of the sympathoadrenal system under the action of neuroleptics haloperidol and sulpiride was studied on the model of immobilization stress in rats. The drugs were shown to possess the effect of the pharmacological correction of hormone content in the adrenals and the level of the neuromediator activity of the adrenergic nerves at different stages of immobilization stress. The data obtained indicate the anti-stress action of the studied neuroleptics. The effect of sulpiride is noted both in the early (the stage of anxiety) and late (the stage of exhaustion) periods of immobilization. The action of haloperidol is mainly limited to the stage of anxiety.
Nonachlazine (2 micrometer) blocked significantly the uptake 1 of endogenic noradrenaline in the myocardial tissues and in adrenergic neurons of vas deferens. The uptake II, as well as the intensity and dynamics of the noradrenaline release were not affected by nonachlazine. These processes resulted in an increase of free noradrenaline concentrations in the synaptic space. The latter seems to be a result of the mediator's passage into the nerve fibers (through axonal membranes) and into the granule, this being due to the nonachlazine-induced block. It is suggested that the metabolic and functional nonachlazine effects are related to the beta-adrenergic receptors stimulation, mediated through the agency of noradrenaline.
By employing spectrofluorometry and quantitative fluorescent histochemistry the norepinephrine (NE) content in the tissue and in the adrenergic nerves of Vas deferens of the rat after depletion of the transmitter's reserves with tyramine and their subsequent replenishment through incubation of the tissue with exogenous NE was measured. The object of investigations was also the influence of antidepressants (phthoracizine and imipramine) and of the cholinolytic spasmolytin (diphacyl) on processes of the NE accumulation. Phthoracizine, impramine and spasmolytin were found to capable of inhibiting accumulation of the exogenous NE in the tissue and in the adrenergic nerves of Vas deferens, provided the mediator is present in the extraneuronal medium in a concentration of 0.5 gamma/ml. When the neurotransmitter was introduced into the medium in higher concentrations (10 gamma/ml) the antidepressents and cholinolytic did not produce the said effect. A correlation of spectrofluorometric and quantitative fluorescent-histochemical findings was observed in cases when the tissue contained less than 50% (i.e. less than 9 gamma/ml) of the total NE reserves.
Fluorescent microscopy and spectrofluorometry of biogenic amines were used to study adrenergic innervation of the dura mater, vas deferens and medullary substance of the adrenals in immobilized rats treated with phenazepam. It was established that phenazepam (1 mg/kg, i. p.) prevented the decrease in the level of the adrenergic transmitter at the stage of anxiety and promoted its stabilization throughout the entire period of body adaptation to immobilization. The stress-protective effect of the drug appeared reduced at the stage of cachexia.
Spectrofluorometric determination of the noradrenaline content in the non-purified fraction of the rat's brain stem synaptosomes and radioisotope method resulted in finding that carbidine is capable to release noradrenaline from the nerve endings. Azabutyron, droperidol and fluphenazine had no noticeable effect on this process. The release of noradrenaline with carbidine depends upon the presence of Ca2+ ions in the medium. This neuroleptic is also capable of intensifying the release of the mediator provoked by the potassium depolarization of the nerve endings.
It was established that single administration to rats of 200 mg/kg of lithium hydroxybutyrate releases noradrenalin from the terminals of hypothalamus adrenergic fibers and increases output of polypeptides in the neurons of supraoptic and paraventricular nuclei of the hypothalamus. After repeated administration of the drug (200 mg/kg) once a day over 6 days) the nuclei showed depressed output of polypeptides.
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