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  • 1
    ISSN: 1432-2072
    Schlagwort(e): Key words Drug abuse ; Stimulant ; Cocaine ; Dopamine ; Monoamine transport ; Self-administration ; Rhesus monkey
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission. Drugs that block dopamine (DA) uptake have generally been found to function as positive reinforcers. Benztropine (BZT) and several of its halogenated analogs have previously been characterized as potent DA-uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. Objectives: The present experiments were designed to examine, in rhesus monkeys, the reinforcing effects of the DA-uptake inhibitor BZT and two chloro-analogs 3’-C1-BZT and 4’-Cl-BZT, and to compare self-administration and binding profiles. Methods: Four rhesus monkeys self-administered cocaine i.v. under a fixed-ratio 10 (FR10) schedule until stable responding was established. Saline, and various doses of cocaine, BZT, and the BZT analogs were then made available for self-administration. Binding of these compounds to monoaminergic and cholinergic sites in monkey brain were determined using standard radioligand binding techniques. Results: Self-administration was maintained by both 3’-C1-BZT and 4’-Cl-BZT, but not by BZT. Results suggested that 3’-C1-BZT and 4’-Cl-BZT were weak positive reinforcers. BZT and analogs bound DA transporters (DAT) with affinities higher than that of cocaine and had affinity for muscarinic binding sites. Conclusions: Surprisingly, high affinity at DATs was associated with weak or no reinforcing effects. The mechanism(s) that may underlie this dissociation between DAT actions and reinforcing effects remains to be established. These data support the proposal that a lead for the discovery of a pharmacotherapeutic agent for cocaine abuse may come from this group of compounds.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Urological research 19 (1991), S. 81-86 
    ISSN: 1434-0879
    Schlagwort(e): Kidney ischemia ; Kidney preservation ; Kidney transplantation ; Glomerular filtration rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Although transplanting rat kidneys is an established microsurgical technique, inulin clearance is abnormally low, due to rejection and/or warm ischemia-induced damage. In the present studies, rejection was avoided by using inbred Brown Norway rats as donors and recipients. Donor kidneys were flushed with ice-cold solutions of various composition (saline, saline + 200 or 400 mM mannitol) and pHs (5.7, 6.4, and 7.4), and the kidneys were kept cold during transplantation into unilaterally nephrectomized recipients. Renal function was assessed by clearance techniques 1 week later. In control rats, with both native kidneys intact, the ratio of inulin clearance, left kidney to right kidney, was 0.99±0.02. In rats with a native right kidney and a transplanted left kidney that had been flushed with saline, the ratio was considerably lower (0.46±0.09). Adding 200 mM mannitol to the saline flush solution increased the ratio (0.89±0.09). In comparison, adding 200 mM mannitol and 5 mM phosphate buffer at pH 7.4 resulted in a somewhat lower ratio (0.80±0.09), whereas adding 200 mM mannitol and 5 mM phosphate buffer at pH 5.7 resulted in a higher ratio, one that was indistinguishable from control (0.97±0.09). Thus, in this latter group, the inulin clearances of the transplanted kidneys were identical to those of the contralateral native kidneys.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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