Biomedical subjects
Publications and source records attributed to R Brus.
In a survey of the pertinent literature the pharmacological and toxicodynamic, effects, metabolism and mechanism of action of diazepam in experimental animals and humans are discussed. Particular attention is paid to the effects of diazepam given during the developmental age on the development and function of the central nervous system in mammals.
Present-day views on the molecular mechanism of ethanol action upon the central nervous system of adult mammals as well as consequences of the brain exposure to ethanol during fetal life, and upon the development and function of this organ in postnatal life are reviewed. Mechanisms of teratogenic effect of ethanol are also discussed.
PGE1 administered in a single dose of 27 nmol intracerebroventricularly (icv) into the rats under urethane anaesthesia caused a long-lasting increase of the blood pressure and tachycardia. Phenoxybenzamine given 60 min before (20 mg/kg ip) blocked the hypertension and tachycardia evoked by PGE1 icv administration. Moreover, reserpine (10 mg/kg ip) given 24 h before PGE1 injection caused similar effects. Previous degeneration of the central adrenergic neurons (6-hydroxydopamine, 2 x 250 micrograms icv) also reduced both exerted effects by PGE1 icv. From the experiments carried out it results that central cardiovascular effects of PGE1 are due to the intact cerebral neurotransmission. These described effects could be common with direct PGE1 action upon adrenergic receptors from indirect effects due to release of noradrenaline by PGE1 in the central nervous system (CNS) in rats.
Levels of 24 free amino acids were estimated in the brain after administration of 5,6-dihydroxytryptamine and 6-hydroxydopamine into the lateral brain ventricles of male Wistar rats. These neurotransmitters caused serotoninectomy and sympathectomy in the diencephalon, striatum, brain stem and medulla, thalamus and hypothalamus, cerebral cortex and cerebellum. The most abundant amino acids in these brain structures were: glutamic acid, serine, aspartic acid, cystine, gamma-aminobutyric acid, glycine, tryptophan and alanine. We detected and quantified changes in the levels of these and other amino acids in the investigated regions of the rat central nervous system, under the influence of these two neurotransmitters.
The influence of verapamil on cardiovascular effects of prostacyclin (PGI2) in rats was examined. PGI2 administered into the lateral brain ventricle (i.c.v.) or intravenously (i.v.) in a dose of 2.7 x 10(-8)mol evoked hypotension and tachycardia. Pretreatment with verapamil in a dose of 2.0 x 10(-5)mol/kg given intraperitoneally (i.p.) diminished hypotensive effect of PGI2 i.c.v. as well as inhibiting the influence of PGI2 i.c.v. and i.v. upon the heart rate. Bolus injection of PGI2 in a dose of 2.7 x 10(-10), 2.7 x 10(-9) or 2.7 x 10(-8)mol evoked biphasic inotropic and chronotropic effects on isolated rat heart. Short-term increase of the contractile force together with bradycardia and afterwards long-lasting decrease of contractility with sustained, slight tachycardia were observed. Verapamil in a concentration of 1.0 x 10(-6)M blocked biphasic inotropic effect and bradycardia after PGI2 administration. Because some central and peripheral cardiovascular effects of PGI2 were inhibited by verapamil, it is concluded that PGI2 may participate in transmembrane calcium ions movements.
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Leukotrienes (LTs) C4 or D4 in a dose of 12 nmoles were administered into the lateral ventricle (i.c.v.) of the rat brain under urethane anaesthesia, and the changes in the blood pressure, heart and respiratory rate were investigated. In other animals the behaviour was evaluated by means of the open field test, and the rectal body temperature was measured. Besides, the content of noradrenaline, 5-hydroxytryptamine and 5-hydroxyindole acetic acid was estimated in different parts of the brain following i.c.v. application of LTs. In mice the antinociceptive effect of LTs in a dose of 1.5 nmoles was examined in the hot plate test; furthermore, the effect of LTs on chlorpromazine catalepsy was measured. Only LTC4 caused a slight rise of the peripheral blood pressure, a decreased respiratory rate and affected the behaviour of rats. Both LTs decreased the rectal body temperature but did not alter the content of biogenic amines in the brain of rats. In mice both LTs did not change the reactivity to thermic pain stimulus; only LTC4 intensified chlorpromazine catalepsy. The results indicate that both LTs exert slight biological effects upon the central nervous system; however, it should be emphasized that LTC4 has a stronger effect.
The experiment was carried out on male guinea pigs exposed to NO2 at a constant concentration of 0.1 ppm 24 h daily for 1, 2.5 and 6 months, or NO2 concentration was increased to 0.5 ppm twice daily, between 7:00 and 8:00 AM and 4:00 and 5:00 PM. After the exposure to NO2 was over the animals were killed by decapitation. The cranium was opened and the brain removed, and afterwards at 0 degrees C the left hemisphere was dissected into discrete areas which were then frozen on dry ice and weighed. The tissues were kept for 2-3 days at -20 degrees C, and afterwards the content of noradrenaline, 5-hydroxytryptamine and 5-hydroxyindole-acetic acid was estimated spectrofluorometrically in examined parts of the brain (thalamus--hypothalamus pons + medulla oblongata hippocampus, cortex frontalis). It was shown that the applied NO2 concentrations brought about slight and nonspecific alterations in the content of the investigated amines in guinea pigs' brain.
Prostacyclin (PGI2) administered i.c.v. into the lateral rat brain ventricle in a dose of 1 and 10 micrograms causes hypothermia, catalepsy as well as a mild analgesic effect. Joint administration of PGI2 along with chloropromazine or morphine produces a greater cataleptic effect than that observed after application of neuroleptics and morphine alone. Cimetidine (CMT) (2 g/kg p.o.) administered 60 min before intraventricular PGI2 injection inhibits hypothermic and cataleptogenic action of the investigated prostaglandin. CMT blocks cataleptogenic effect of chloropromazine and morphine as well as the combination of these two substances with PGI2. CMT inhibits the cataleptogenic effect of haloperidol, but it does not block the catalepsy induced by joint administration of haloperidol and PGI2. CMT does not modify the analgesic action of PGI2. The results indicate that H2 receptors take part in some central pharmacological effects of PGI2 in rats.
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D-Ala2-met-enkephalinamide (DAMEA) in ethyl urethane anesthetised rats increased the blood pressure, decreased heart rate and frequency of respirations. DAMEA could act centrally as well as peripherally after the penetration from the cerebro-spinal into the blood stream. These effects were blocked by naloxone. 6-Hydroxydopamine inhibited the circulatory and respiratory action of DAMEA. 5,6-Dihydroxytryptamine reversed this action of DAMEA. It is suggested that central presynaptic catecholamine and serotonin neurons modulate the central effects of DAMEA on the circulatory system and respiration in rats.
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PGI2 1 or 10 micrograms iv caused a decrease of blood pressure and bradycardia in rats. PGI2 administered into lateral ventricle of rat brain [icv] exerted hypotensive effect and tachycardia. PGI2 10 micrograms icv increased histamine level in the hypothalamus and cortex of rat's brain, but it did not influence histamine content in the blood. Cimetidine [CMT] given 60 min earlier per os inhibited bradycardia caused by PGI2 iv administration and diminished hypotensive action and tachycardia produced by PGI2 icv.
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The effect of prostaglandins (PGs) F1 alpha, F2 alpha, E2, D2, A1, B1 and I2 administered intracerebroventricularly (i.c.v.) in mice in a dose of 1 microgram on catalepsy induced by chloropromazine (2.5 mg/kg i.p.) was examined. It was demonstrated that only PGF2 alpha reduced significantly the chloropromazine induced catalepsy, while PGI2 intensified it. The other examined PGs were without any effect on chlorpromazine catalepsy. The results show the modifying role of some PGs on chloropromazine effects on central dopaminergic receptors in mice.
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