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  • 1
    ISSN: 1432-2072
    Keywords: LM 5008 ; Quipazine ; Metachlorophenylpiperazine ; d-Fenfluramine ; Serotonin uptake ; Serotonin release ; Serotonin receptor ; Anorexia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 4-(3-Indolyl-2-ethyl)piperidine (LM 5008), 2-(1-piperazinyl) quinoline (quipazine), and metachlorophenylpiperazine (mCPP) were studied for their ability to affect serotonergic mechanisms in vitro. Their relative potency in inhibiting serotonin (5-HT) uptake in vivo and reducing food intake in rats was also examined. mCPP was very potent in displacing 3H-5-HT bound to brain membranes (IC50, 6.2×10-7 M), followed by quipazine, which showed an IC50 of 3.8×10-6 M. LM 5008 was the least effective with an IC50 of 3.6×10-5 M. mCPP and quipazine were less potent than d-fenfluramine in releasing 14C-5-HT from brain synaptosomes, while LM 5008 caused no significant effects at a concentration of 10-5 M. Conversely, both in vitro and in vivo studies on 5-HT uptake showed that LM 5008 was the most potent compound in inhibiting 5-HT uptake and mCPP the least potent. Since a 50% reduction of food intake was not reached even with a dose of LM 5008 27-times higher than the ED50 for inhibiting 5-HT uptake in vivo, it is suggested that even marked inhibition of 5-HT uptake at central synapses is not sufficient per se to trigger serotonin-dependent anorexia in the rat. Increased release and/or direct stimulation of post-synaptic receptors may be necessary to obtain this effect. This could be of interest for developing new agents which can cause anorexia by interacting with brain serotonin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Buspirone ; Haloperidol ; Sulpiride ; Anxiolytics ; Punished responding ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of buspirone, haloperidol and sulpiride were compared with diazepam in two experimental models of anxiety in rats. In a conflict test, 0.6 and 1.2 mg/kg buspirone, 0.05 and 0.10 mg/kg haloperidol and 0.5 mg/kg sulpiride significantly increased punished responding. Buspirone 1.2 and 2.5 mg/kg significantly reduced the number of unpunished responses while haloperidol and sulpiride at the doses tested had no effect. Effects on punished responding were seen in a narrow dose range and were less pronounced with these drugs than with diazepam. Similar results were obtained with rats', activity in the two-compartment exploratory test. At doses causing no change in the locomotion of rats in photocell activity cages, buspirone (0.1 mg/kg), haloperidol (0.025–0.100 mg/kg) and sulpiride (0.5–1.0 mg/kg) significantly increased the number of crossings between the two compartments. Again, the peak effects were small when compared with the effect of diazepam and the active dose range was very narrow. Apomorphine 0.2 mg/kg SC significantly counteracted the effect of 0.1 mg buspirone and 1.0 mg/kg sulpiride in the two-compartment exploratory test with no effect on 2.5 mg/kg diazepam. The data show that buspirone, in a narrow dose range, shows disinhibitory effects in experimental models of anxiety. Similar effects are shown by low doses of haloperidol and sulpiride. It is suggested that buspirone and sulpiride produce these disinhibitory effects by blocking particular dopamine receptors in the brain, possibly those located in the nerve terminals, but it is likely that other mechanisms, particularly serotonin, are involved in the effects of buspirone in anxious states.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 308 (1979), S. 159-163 
    ISSN: 1432-1912
    Keywords: Serotonin ; Receptor stimulation ; Metachlorophenylpiperazine ; Anorexia ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3×10−6 M and 5.8×10−6 M respectively. Dopamine uptake was lesss affected by meta-chlorophenylpiperazine (IC50 of 2.2×10−5 M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist in the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Neurotensin ; Dopamine ; Mesolimbic system ; Antidepressant activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Locomotor activity and behaviour in the forced swimming test were examined in rats which had received neurotensin (0.5–5.0 µg) in the ventral tegmental area. Doses of 5 µg neurotensin but not lower increased the locomotor activity for at least 2 h. At 0.5 and 1.0 µg neurotensin significantly increased the time the animals spent in struggling with no changes in general motor activity (swimming). The effect of 1.0 µg neurotensin on struggling was completely antagonized by 0.5 µg (−)-sulpiride administered in the posterior nucleus accumbens. The results suggest that activation of the mesolimbic dopamine system through administration of neurotensin in the ventral tegmental area produces antidepressant-like effects. The significance of these findings for a role of endogenous neurotensin in depression remains to be clarified.
    Type of Medium: Electronic Resource
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