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  • Antinociception  (4)
  • Adenosine deaminase  (2)
  • Mammals  (2)
  • 1
    ISSN: 1432-2072
    Schlagwort(e): Nicotine ABT-418 ; Antinociception ; Hypothermia ; Locomotor activity ; Drug discrimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract ABT-418, a novel cholinergic ligand, was reported to possess potent cognitive-enhancing and anxiolytic properties in animal models with reduced side effects (Decker et al. 1994; Garvey et al. 1994) suggesting selectivity of effects. In this study, the binding properties of ABT-418 to [3H]-nicotine sites were evaluated and its pharmacology investigated in different tests in laboratory animals. ABT-418 binds with high affinity to3H-nicotine binding sites in the brain with, however, a Ki (6 nM) less than that of nicotine (four-fold). In addition, it acts as a full nicotinic agonist in producing hypomotility, hypothermia and antinociception in mice and engendering nicotine-like responding in rat drug discrimination. The potency of ABT-418 is three to four times less than that of nicotine in all of the animal models, except for hypothermia. In addition, its behavioral effects are completely blocked by mecamylamine, a non-competitive nicotinic antagonist. Although activation of nicotinic receptors by ABT-418 produced several behavioral and pharmacological effects, our results do not suggest high selectivity of different effects as reported by Decker et al. (1994) and Garvey et al. (1994). However, it should be noted that we did not perform some of these tests that produced effects at low doses (Decker et al. 1994) and additional pharmacological studies are needed to establish its selectivity at multiple nicotinic receptors.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 117 (1995), S. 67-73 
    ISSN: 1432-2072
    Schlagwort(e): Nicotine dihydro-β-erythroidine ; Antinociception ; Calcium ; Mecamylamine ; Mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The comparative in vivo pharmacology of mecamylamine and dihydro-β-erythroidine (DHβE) in mice was studied. Modulation of the behavioral effects (antinociception, hypomotility, motor impairment and hypothermia) of nicotine in mice by DHβE and mecamylamine were carried out. After SC administration, DHβE and mecamylamine were nearly equipotent in blocking nicotine's effects except for antinociception, in which mecamylamine was clearly more potent. Intrathecal injection of DHβE was also effective in blocking the antinociceptive effect of nicotine. In vivo interaction of DHβE with calcium and calcium channels, involved in the central actions of nicotine, showed that intrathecal administration of DHβE failed to reduce the antinociception induced by diverse drugs which increase intracellular calcium such as thapsigargin, (±)-BAYK 8644 and calcium, indicating that this antagonist does not affect calcium-dependent mechanisms involved in antinociception. On the other hand, mecamylamine blocked the antinociceptive effect of the calcium modulatory drugs, suggesting that it may be acting on calcium-dependent mechanisms involved in the intracellular signaling process. We conclude that DHβE, a nicotinic neuromuscular antagonist, is able to block some of the central actions of nicotine after systemic and intrathecal administration. The mechanism of blockade is different from that of mecamylamine, a classical ganglionic antagonist, and may involve a direct action of DHβE on nicotine receptor.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 111 (1993), S. 106-108 
    ISSN: 1432-2072
    Schlagwort(e): Nicotine ; Dopamine antagonists ; Hypoactivity ; Hyperactivity ; Antinociception ; Mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pretreatment with ineffective doses of the D1 antagonist SCH23390 but not the D2 antagonist sulpiride reduced hyperactivity induced by nicotine in mice habituated to the test cage. On the other hand, the D1 and D2 antagonists were ineffective in blocking nicotine-induced hypoactivity in naive mice. Finally, SCH23390 and sulpiride did not block the antinociception induced by nicotine. Our data indicate that the dopamine receptors D1 and D2 are not involved in all the central effects of nicotine in mice, but seems to be a substrate for locomotor activation induced by nicotine under specific experimental conditions.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 119 (1995), S. 282-290 
    ISSN: 1432-2072
    Schlagwort(e): Radial-arm maze ; Δ9-tetrahydrocannabinol (Δ9-THC) ; CP-55,940 ; WIN-55,212-2 ; Anandamide ; Cannabidiol ; Hippocampus ; Antinociception ; Catalepsy ; Rectal temperature
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of Δ9-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED50=0.13 mg/kg). Δ9-THC and WIN-55,212-2 disrupted mazechoice accuracy at equipotent doses (ED50 values =2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of Δ9-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED50=8 µg/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1435-1803
    Schlagwort(e): Adenosine deaminase ; microdialysis ; micropig ; myocardial blood flow ; pentostatin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In order to examine the relationship between local adenosine concentrations before, during, and after ischemia and the extent of ischemic myocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60′ coronary artery occlusion (CAO) and 3h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inosine and hypoxanthine), myocardial infarct size, and myocardial blood flow (MBF) were determined in control animals (n=6), animals preconditioned with a single 10′ cycle of CAO and REP (PC, n=6), and those treated with the adenosine deaminase inhibitor pentostatin (n=6, 0.2 mg/Kg IV 30′ prior to CAO). The brief PC occlusion resulted in a transient but significant increase in dialysate ADO (6.7±1.8 μM vs. 0.67±0.1 μM at baseline). Pentostatin administration had no significant effect on either dialysate nucleosides or MBF at baseline. During the 60′ CAO, dialystate ADO increased in control animals. In PC animals, however, dialysate ADO during CAO was lower than control. Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62±30.2 μM vs. 16.31±2.1 μM at 60 min of ischemia). Pentostatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating inhibition of adenosine deaminase activity. There were no significant differences in MBF between groups at any time point. Following 3 h REP, infarct size was 35.4±5.5%, 8.1±1.5% and 8.3±1.8% of the region at control, PC, and pentostatin groups, respectively. These data suggest that marked increase in ISF ADO during CAO, may be as effective in reducing INF as a modest increase in ISF ADO prior to prolonged CAO.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Basic research in cardiology 90 (1995), S. 176-183 
    ISSN: 1435-1803
    Schlagwort(e): Adenosine deaminase ; adenosine ; myocardial stunning ; sonomicrometers ; microspheres ; dog
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study was to determine if adenosine deaminase inhibition with pentostatin could improve postischemic contractile dysfunction (stunning) in open-chest anesthetized dogs. All animals underwent 15 min of coronary occlusion followed by 3 h of reperfusion preceded by an intravenous bolus of either 0.2 mg/kg of pentostatin (n=8) or saline (n=7). Sonomicrometers were plced in the ischemic area and were used to measure systolic wall thickening before, during, and after occlusion of the left anterior descending artery. Myocardial blood flow was measured with tracer labeled microspheres at baseline, 10 min of occlusion and at 1 h of reperfusion. Both groups were equally dyskinetic during occlusion (−21±5% of baseline thickening in the controls and −28±8% in the pentostatin group). The pentostatin group, however, demonstrated better contractile function at all time points during reperfusion, which was significantly different from the control group at 3 h of reperfusion. The improvement in regional function in the pentostatin group was not due to significant disparities in hemodynamic variables, size of the region at risk, or in collateral blood flow. These results indicate that pentostatin can ameliorate the severity of myocardial stunning, an effect we propose is due to increasing endogenous levels of adenosine during the ischemic interval. Although significant improvement was detected with pentostatin, the improvement was modest compared to controls, suggesting that the utility of inhibiting adenosine deaminase to modify regional mechanical stunning is limited.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 164 (1975), S. 133-144 
    ISSN: 1432-0878
    Schlagwort(e): Bladder body ; Mammals ; Musculature ; Innervation ; Electron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution and structure of the nerves supplying the muscle of the body of the bladder in mammals such as the mouse, guinea-pig, rabbit, cat and dog was compared with that previously demonstrated in the rat. The muscle of the arterioles located between the muscle bundles is innervated by a fine perivascular plexus and the nerves forming the muscular plexus can be divided into inter-and intra-fascicular components. Terminals containing variable but usually small numbers of clear and large dense-cored vesicles are particularly numerous in the interfascicular nerves and the intrafascicular nerves are characterised by large numbers of terminals with the features of those of cholinergic axons. In addition to many small clear vesicles, the cholinergic terminals contained some small dense-cored vesicles, and it is suggested that, as in the rat, these contain a second transmitter which is released with acetylcholine at the terminals during impulse transmission. Adrenergic terminals are more common in the muscular plexuses of the guinea-pig, dog and cat than in those of the other animals studied and there is evidence for the presence of two types of such terminal in the nerves. Of these, one contains a much smaller proportion of small vesicles with dense cores and many more large dense-cored vesicles than the second, and the possibility of a relationship between such terminals and those of short adrenergic neurones and neurones associated with non-adrenergic patterns of impulse transmission is discussed.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 160 (1975), S. 515-524 
    ISSN: 1432-0878
    Schlagwort(e): Ureteric innervation ; Mammals ; Interspecies differences ; Electron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution and structure of the ureteric nerves in a small series of mammals was compared with that previously demonstrated in the rat. There was marked interspecies variation in the extent to which the nerves penetrated the wall of the ureter and in the degree of development of the deep submucous plexus. In animals with a highly developed deep submucous plexus, terminal arterioles frequently passed through the muscle coat before breaking up into capillaries. These vessels were surrounded by a fine periarteriolar plexus and were accompanied in their course through the muscle coat by one or more branches of the adventitial nerves. Intramuscular nerves not related to arterioles contained few axons with terminals classifiable as either adrenergic or cholinergic, and in animals in which the muscle cells were arranged in fascicles rather than in sheets, the nerves were typically interfascicular in position. As in the rat, only the periarteriolar plexuses contained large numbers of adrenergic axons. Cholinergic axons were generally few, but were not uncommon in the deep submucous plexus when this was well-developed. The majority of the terminals encountered in the intramural nerves contained variable and usually small numbers of both clear and large dense-cored vesicles. The relationship between these terminals and those defined in the submucous nerves of the rat ureter was discussed and it was suggested that the marked variations in the diameter of the axons in the terminal areas and in the number of vesicles in the terminals were related to the effects of the mechanical and other derangements which occur during processing.
    Materialart: Digitale Medien
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