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  • Electronic Resource  (4)
  • Adenosine deaminase  (2)
  • Drug discrimination  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Comparative pharmacology of nicotine and ABT-418, a new nicotinic agonist (1995)
    Springer
    Psychopharmacology 120 (1995), S. 483-490 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ABT-418 ; Antinociception ; Hypothermia ; Locomotor activity ; Drug discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245822
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacological specificity of Δ9-tetrahydrocannabinol discrimination in rats (1995)
    Springer
    Psychopharmacology 118 (1995), S. 419-424 
    Details
    ISSN: 1432-2072
    Keywords: Δ9-THC ; Drug discrimination ; Benzodiazepines ; Specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While many previous studies have shown that a variety of cannabinoids substitute and cross-substitute for Δ9-tetrahydrocannabinol (THC) in drug discrimination procedures, few have systematically examined potential THC-like effects of non-cannabinoid compounds. The purpose of the present study was to delineate further the pharmacological specificity of THC discrimination. Rats were trained to discriminate THC (3.0 mg/kg) from vehicle. Following determination of a dose-effect curve with THC, substitution tests with selected compounds from a variety of pharmacological classes, includingl-phenylisopropyl adenosine, dizocilpine, dextromethorphan, clozapine, buspirone, MDL 72222, muscimol, midazolam and chlordiazepoxide, were performed. Whereas THC produced full dose-dependent substitution, substitution tests with non-cannabinoid drugs resulted in less than chance (50%) levels of responding on the THC-appropriate lever, with the exception of (+)-MDMA (2.5 mg/kg, 50%) and diazepam (3.0 mg/kg, 67%). These results are consistent with those of previous studies and suggest that the discriminative stimulus effects of THC exhibit pharmacological specificity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245942
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size (1997)
    Springer
    Basic research in cardiology 92 (1997), S. 240-251 
    Details
    ISSN: 1435-1803
    Keywords: Adenosine deaminase ; microdialysis ; micropig ; myocardial blood flow ; pentostatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00788519
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning in dogs (1995)
    Springer
    Basic research in cardiology 90 (1995), S. 176-183 
    Details
    ISSN: 1435-1803
    Keywords: Adenosine deaminase ; adenosine ; myocardial stunning ; sonomicrometers ; microspheres ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00789447
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    Paper (German National Licenses)
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