Impairment of working memory by neuronal degeneration with NMDA in rat hippocampal CA-1.

Rats were trained on a three-panel runway task prior to injections of N-methyl-D-aspartate (NMDA; 40nmoles/µl/side) into the dorsal hippocampus. One week after the treatment, animals did not show any change in the number of errors on the first runway trial (reference memory), with one correct white and two incorrect black panels at each choice point, whereas they showed a marked increase in the number of errors on the following (2nd-6th) trials (working memory) with all black panels. The memory deficit persisted at least for 10 days.

Dual activation by lisuride of central serotonin 5-HT(1A) and dopamine D(2) receptor sites: drug discrimination and receptor binding studies.

To investigate central serotonergic (5-HT) and dopaminergic (DA) actions of lisuride, the discriminative properties of lisuride (0.05mg/kg, i.p.

Effect of water-soluble contrast medium on the lung in rats. Comparison of iotrolan, iopamidol, and diatrizoate.

Aspiration is a serious complication of oral contrast media (CM). The authors investigated the effects of iotrolan, iopamidol, and diatrizoate in rats' lungs. To quantify the lung damage induced by CM, pulmonary water and hemoglobin contents were determined.

[Tissue distribution of red blood cells treated with X-ray contrast media in rats].

Tissue distribution of red blood cells (RBC) that were treated with X-ray contrast media was investigated in rats. The contrast medium mixed with an equivolume of 51Cr-labelled RBC was administered to the internal carotid artery in a dose of 200 microliters/rat; and the radioactivity in the brain, lung and spleen were determined. The contrast medium mixed with an equivolume of blood was administered to the right atrium in a dose of 4 ml/kg, and the hemoglobin content in the lung and changes in pulmonary and circulatory functions were determined.

Role of red blood cell deformation in toxicity of contrast media in cerebral angiography.

The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB).

[Neurotropic effects of non-ionic contrast media].

Effects of non-ionic contrast media on the central nervous system were compared in order to clarify any differences due to the side-chain structures among iopamidol, iotrolan, iocibidol, iohexol, iopromide, iosimide and metrizamide. The study included a primary screening test based on Irwin's method, antielectric convulsive tests using mice, measurement of the blood pressure using rats and electroencephalography using rats and rabbits. The general behavior of mice in the primary screening test revealed that tolerance to iopamidol, iotrolan and iocibidol was excellent; that to iopromide and iohexol was moderate; and that to iosimide and metrizamide was poor.

A possible mechanism for the neural adverse reactions caused by metrizamide.

Causality of the metrizamide-induced neural adverse effects was explored among the effects on behavior, electroencephalogram (EEG), and brain glucose utilization in rats. Iotrolan, a new myelographic contrast agent, was used as a reference substance throughout the study. Supracortical subarachnoidal administration of metrizamide caused, within a few minutes, symptoms of sedation and anxiety, which were accompanied by appearance of slow wave or flattening in EEG not only of the cortex, but also of the regions of the hippocampus and thalamus.

The effect of a selective phosphodiesterase inhibitor, rolipram, on muricide in olfactory bulbectomized rats.

In order to evaluate the potential usefulness of the drug as an antidepressant, acute and chronic effects of rolipram, a selective inhibitor of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase were investigated on muricide in olfactory bulbectomized (OB) rats. Upon single administration to OB rats, rolipram at a dosage of 1 mg/kg body weight suppressed the muricide for 2 hr after its administration. As a consequence of daily administration of rolipram, however, the incidence of muricide at 24 hr after the administration was decreased, and more than 60% of the rats did not exhibit the muricide on the 12th day.

[Central dopaminergic function in stroke-prone spontaneously hypertensive rats (SHRSP): II. Effects of chronic treatment with lisuride on the impaired swimming ability].

Eight month-old SHRSP were treated s.c. with lisuride (50 micrograms/kg per day) for 5 weeks to examine the effect of the central dopaminergic agonist on the deterioration of swimming ability that occurred and progressed under persistent hypertension.

[Central dopaminergic function in stroke-prone spontaneously hypertensive rats (SHRSP): I. Alteration of locomotor activity and swimming ability].

The possible alteration of central dopaminergic (DA) function, which accompanies the development and persistence of hypertension, was studied in SHRSP by measuring the lisuride-induced locomotor activity and the swimming ability. 1) When administered at a dosage of 50 micrograms/kg, lisuride, a DA agonist, induced significant increases of the locomotor activity in one- and 2-month-old Wistar Kyoto rats (WKY), but not in the 6 month-old rat. Differing from the response of WKY, SHRSP showed only a moderate increase in the locomotor activity at the age of one month (means of systolic blood pressure: 128 mmHg) and apparently no increase at the age of 2 months (176 mmHg).

[General pharmacology of lisuride hydrogen maleate--actions on isolated organs, especially on smooth muscles].

Pharmacological actions of lisuride hydrogen maleate (lisuride) were studied by using isolated organs. 1) Lisuride at 2.2 microM exerted a negative chronotropic effect on guinea-pig atria, the effect being antagonized completely by 2.

[Suppressive effects of lisuride on the synthesis, release and metabolism of dopamine in rat brain].

Effects of lisuride, a central dopaminergic agonist of the ergot type, on the biosynthesis, release and metabolism of dopamine at the dopaminergic nerve terminals of the rat brain were studied under several experimental conditions. 1) In the rat whose impulse flow of dopamine neurons and the activity of aromatic amino acid decarboxylase were inhibited by the pretreatment with gamma-butyrolactone and with 3-hydroxybenzylhydrazine (NDS 1015), respectively, DOPA formation in the neostriatum and limbic forebrain were decreased significantly by the s.c.

Some characteristics of hydrogen- and alkylhydroperoxides metabolizing systems in cardiac tissue.

The effect of hydroperoxides on the cardiac tissue was studied by using hemoglobin-free perfused rat heart. Ethylhydroperoxide was degraded mainly through the glutathione peroxidase system of the heart at a maximal rate of about 1.2 mumol/min per g wet wt.

[Effects of an ergot derivative, lisuride, on the central nervous system -- stimulatory effect on local cerebral glucose utilization in the rat].

Effects of lisuride, a central dopamine and serotonin agonist of the ergot type, on local cerebral glucose utilization were studied in conscious, anesthetized, and substantia nigra-lesioned rats using the autoradiographic 2-deoxyglucose method. In the conscious rat, lisuride produced dose-dependent (0.05-0.

[Effects of an ergot derivative, lisuride, on the central dopaminergic system -- studies of behavioral pharmacology].

The central dopaminergic (DA) activity of lisuride hydrogen maleate (lisuride) was investigated from the view point of behavioral pharmacology in rats and mice. Lisuride exhibited a biphasic action on locomotor activity in mice and rats; with low doses lisuride caused hypomotility, whereas higher doses produced locomotor stimulation. The hypomotility induced by lisuride (0.

Regioselectivity and reactivity in microsomal hydroxylation of a series of N-acyl- and N-sulfonylamines in rats.

Regioselectivity and overall reactivity in the hydroxylation of a series of substituted N-benzoyl- and benzenesulfonyl aliphatic and alicyclic amines with rat liver microsomes were investigated. The hydroxylation occurred predominantly at the position gamma to the nitrogen atom. para-Alkyl-substituted benzoylamines were hydroxylated at both the benzylic positions as well as the gamma-position, whereas para-substituted benzenesulfonylamines were hydroxylated mainly at the benzylic position.

Biotransformation of lisuride in the hemoglobin-free perfused rat liver and in the whole animal.

Isolated rat livers were perfused with an oxygenated saline medium containing 14C-lisuride. Metabolites obtained in the bile and the perfusate were characterized as the glucuronide of hydroxylisuride and hydroxy, 2-oxo, monode-ethyl, dide-ethyl, N6-demethyl and monode-ethyl-N6-demethyl derivatives of lisuride. In addition, the metabolite patterns were examined in various tissue homogenates in vitro and also in the rat in vivo.

The pharmacokinetics of lisuride hydrogen maleate in rat, rabbit and rhesus monkey.

The pharmacokinetics of lisuride hydrogen maleate (LHM) were investigated in rat, rabbit and rhesus monkey. Experiments were designed to meet not only the requirements of drug registration but also to serve other preclinical disciplines (toxicology, pharmacology). LHM is absorbed almost completely at a dose level of 100-250 micrograms/kg.

Stimulatory action of lisuride on dopamine-sensitive adenylate cyclase in the rat striatal homogenate.

Effect of lisuride, an ergot derivative of isolysergic structure, on dopamine-sensitive adenylate cyclase was studied in the homogenate of rat corpus striatum. Stimulatory action of lisuride, similar to the actions of dopamine and apomorphine, on striatal adenylate cyclase was potentiated significantly by guanosine triphosphate (GTP) and by guanyl-5'-yl imidodiphosphate (GMP-PNP), although with lisuride alone, there was only a slight stimulation. The maximal stimulation attained in the presence of GTP corresponded to about 1.

[Chemical structure biliary excretion of iodine-containing contrast agents in hemoglobin-free perfused rat liver and in vivo (author's transl)].

Pharmacokinetical properties of eight triiodobenzene derivatives, X-ray contrast agents, were studied in the hemoglobin-free perfused rat liver with emphasis on the structural relation to biliary transport. With chemical modification of the basic structure, these agents showed different characteristics in the processes of diffusion into hepatocytes, accumulation in the cells and active transport into the bile, and were separated into four groups; [I]: Iotroxic acid (1), Iodipamic acid (2), Iodoxamic acid (3), and Ioglycamic acid (4) which showed faster rates of diffusion into hepatocytes [(1) greater than or equal to (2) greater than (3) greater (4)] and also of biliary excretion [(1) greater than (2) greater than (4) greater than (3)], [II]: Diatrizoic acid and Metrizamide showed poor diffusion and biliary excretion, [III]: Iopodic acid showed the highest permeability into and accumulation in hepatocytes with little biliary excretion, [IV]: ZK73 215 was slowly transported into the bile, yet, showed little permeation through the cell membrane. Characteristics of (1), (2) and (3) observed in the perfused liver were, in principle, confirmed in the pharmacokinetical profile observed in vivo.

[Biliary transport of organic anions in the isolated hemoglobin-free perfused rat liver (author's transl)].

Mechanisms involved in the biliary excretion of organic anions were investigated in hemoglobin-free perfused rat liver using iotroxic acid as a test substance. The process of biliary excretion in this system can be separated into three elemental processes, i.e.