[Test of the statistical reciprocal action of ethyl alcohol and dimethyl sulfoxide in animal research].
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Analysis of Variance↗
Biomedical subjects
C Köhler
Publications and source records attributed to C Köhler.
[Telemetric study on heart disease patients during swimming].
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Adult↗
Electrophysiological interactions between carbachol and class I antiarrhythmic drugs (lidocaine, quinidine)--experimental studies in rabbit atrial myocardium.
UNLABELLED: Cholinergic agents exert no direct effect on the fast Na+ inward current but may influence the binding characteristic of class I antiarrhythmic drugs in atrial myocardium by shortening the action potential (AP) duration or by increasing the resting potential (RP). In order to examine such possible interactions we performed experiments using conventional intracellular microelectrodes on isolated preparations of rabbit atrial myocardium (Ke 2.7 mM, temperature 32 degrees C). At first the influence of the cholinergic agent carbachol (1 mg/l = 6.7 x 10(-6) M) on the RP and AP was examined at different stimulation rates (1.0, 2.5, and 3.3 Hz). Thereafter measurements were repeated under the influence of lidocaine (10 mg/l = 2.2 x 10(-5) M) or quinidine (5 mg/l = 2.2 x 10(-5) M) alone and in combination with carbachol (1 mg/l). RESULTS: (statistically significant differences, p less than 0.05): Carbachol increased the RP by about 10 mV and shortened the AP by about 60%. The maximal upstroke velocity of the AP (Vmax) was not significantly altered at 1.0 and 2.5 Hz, but increased under carbachol at 3.3 Hz. After addition of carbachol to the lidocaine-containing solution, Vmax increased to its control level at all stimulation rates. In experiments with quinidine, Vmax also increased after addition of carbachol but remained significantly below the control values. CONCLUSIONS: Carbachol effects on Vmax are most likely attributable to earlier recovery (caused by the shortening of the AP) and to faster recovery kinetics (due to hyperpolarization). The attenuation of the class I effect of lidocaine by carbachol can thus be considered mainly a consequence of the shortening of the inactivated state which results in a reduced affinity of lidocaine to its receptor and allows earlier dissociation of the drug. Minor binding of the drug due to hyperpolarization may play the major role in interactions between carbachol and quinidine.
Action Potentials↗
Lesions in Guddesn's tegmental nuclei produce behavioral and 5-HT effects similar to those after raphe lesions.
Lesions largely restricted to the dorsal and ventral tegmental nuclei of Gudden (GTN) produced several effects similar to those seen after midbrain raphe lesions. GTN lesions significantly reduced the 5-hydroxytryptamine (5-HT) concentration of the diencephalon (31 percent), hippocampus (59 percent), and remaining portion of the telencephalon (29 percent). Striatal 5-HT, however, was not affected. GTN lesions enhanced activity in an enclosed field and facilitated two-way avoidance acquisition. Pain sensitivity as measured by the flinch-jump method was not affected. These results suggest that the GTN may be the origin of ascending 5-HT fides and may be involved in the regulation of activity level and the adaptation of an animal to aversive situations. Thus, some of the behavioral and 5-HT effects of lesions in the midbrain raphe nuclei may be due to their involvement of the GTN and associated pathways.
Animals↗
Presence of NADPH-cytochrome P450 reductase in central catecholaminergic neurones.
The cytochrome P450-containing mixed function oxidases metabolize a variety of endogenous and exogenous compounds including drugs, carcinogens, fatty acids and steroids. Mixed function oxidases have been detected in several tissues, including brain. The enzyme system consists of a lipid fraction (phosphatidylcholine), cytochrome P450 and NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase has been purified to apparent homogeneity and demonstrated to supply reducing equivalents from NADPH to cytochrome P450 (refs 5-7). Detection of NADPH-cytochrome P450 reductase thus represents an indirect means of demonstrating the presence of cytochrome P450. Although the role of cytochrome P450 in the central nervous system (CNS) is not known, it may include such different functions as metabolism of xenobiotics, aromatization of androgens to oestrogens and the formation of catecholoestrogens. Despite the potentially very important role(s) of cytochrome P450 in brain function, its exact regional distribution remains essentially unknown. Using a specific antibody against rat liver NADPH-cytochrome P450 reductase in combination with immunohistochemical techniques, we have now localized this enzyme to define catecholamine (CA)-containing structures of the rat and monkey brain.
Animals↗
[Remoxipride, a selective antagonist of dopamine D2 receptors, in the treatment of delusional psychoses].
Remoxipride, a substituted benzamide, is a new antipsychotic agent which differs from classical neuroleptics in several ways. It has a selective action on the dopamine D2 receptors in the brain and little effect on a variety of other receptor types including serotonin, noradrenaline, acetylcholine and histamine receptors. This implies advantages over classical neuroleptics which have less selective modes of action and subsequently increased propensities to cause side effects. The pharmacokinetics of remoxipride are uncomplicated. The drug is rapidly absorbed, plasma levels increase with dose, and elimination is via urinary excretion. No clinically significant drug interactions have been found. Remoxipride has been shown to be as effective in the treatment of schizophrenic patients as haloperidol in both short and long term double-blind trials. Both positive and negative symptoms are improved. However, remoxipride shows advantages over haloperidol in that the incidences of extrapyramidal symptoms and increased plasma prolactin concentrations are lower in remoxipride recipients. There are no clinically relevant adverse effects on chemistry, haematology or cardiovascular variables.
Adult↗
Autoradiographic quantitation and anatomical mapping of 125I-galanin binding sites in the rat central nervous system.
The distribution of 125I-galanin binding sites in the rat central nervous system was studied by the use of autoradiography, and the amount of peptide bound was determined by the use of microdensitometry. The amount of 125I-galanin bound in various CNS regions ranged from non detectable to 0.40 pmol per gramme tissue at a concentration of 1.5 nM 125I-galanin. The anatomical mapping revealed high density of binding sites in the telencephalon, where labelling was seen in the entorhinal, perirhinal and piriform cortices, in most septal nuclei, in the amygdala and in the hippocampal formation. In the diencephalon binding sites were densely accumulated in the hypothalamus, including the median eminence and periventricular nucleus as well as in the dorsal and medial thalamic nuclei. In the mesencephalon binding sites were seen in many nuclei including the dorsal raphe nucleus, the periaqueductal central grey and pars compacta of the substantia nigra. The pons/medulla revealed high density of binding sites in the locus coeruleus, parabrachial nuclei and in the dorsal vagal complex, while binding in the spinal cord was seen in laminae I, II and X as well as in the intermediolateral horn. The distribution of 125I-galanin binding sites corresponded well to the localization of the peptide as revealed in several earlier immunohistochemical and radioimmunoassay studies, as well as to several previously reported effects of galanin on central autonomic functions.
Animals↗
Autoradiographic mapping of galanin receptors in the monkey brain.
The distribution of specific binding sites for the peptide galanin was studied in the monkey brain by using 125I-galanin and the method of quantitative in vitro autoradiography. The binding to tissue sections was found to be rapid, reversible and saturable with a calculated Bmax of around 13 fmol mg-1 tissue in cortical regions and a KD ranging between 0.39 and 0.22 nM in different brain regions. Specifically bound 125I-galanin was detected in a number of brain regions throughout the rostrocaudal axis of the monkey brain. More specifically, the majority of the 125I-galanin binding sites were present in the basal forebrain (e.g. olfactory tubercle, lateral septal nuclei, nucleus accumbens, substantia innominata and the basal nucleus of Meynert), the amygdala (e.g. the lateral, medial accessory and central nuclei), the amygdala-hippocampal area, hypothalamus (e.g. the anterior hypothalamic area, the ventro-medial hypothalamus and the zona incerta), as well as in certain brain stem cell groups such as the substantia nigra (pars compacta), locus coeruleus, central grey substance, parabrachial nucleus, sensory and motor nuclei of the trigeminal nerve and the dorsal vagal complex. In the neocortex, highest binding density occurred in layer 4 of all neocortical fields, except in the visual cortex where the highest densities occurred in layers 4cb, 5a and 6. Major fibre tracts such as the fimbria and the stria terminalis also contained high densities of 125I-galanin binding sites. Areas poor in, or lacking, specific 125I-galanin binding sites included the basal ganglia, the thalamus, the mammillary bodies, the cerebellum, and the reticular formation of the brain stem. The pattern of galanin receptor distribution in the monkey brain reported here closely resembles that observed for galanin receptors and galanin-immunoreactive preterminal processes described previously in the rat brain. An exception, however, was neocortex, where in the rat neither 125I-galanin binding nor galanin-positive fibres have been observed. The present findings may indicate a close association between galanin receptors and nerve terminals containing galanin immunoreactivity in the monkey brain and implies important role(s) for galanin in neurotransmission in the monkey central nervous system.
Animals↗