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  • 1
    ISSN: 1420-9071
    Keywords: Platelets ; 5-HT ; LSD binding ; neuroleptics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, theB max of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene δ treatment ‘up-regulates’ platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased theB max of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 101 (1990), S. 49-53 
    ISSN: 1432-2072
    Keywords: Carbamazepine ; 5-HT ; Behaviour ; Synthesis ; Release ; Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropy-laminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of post-synaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed byl-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 µM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex. These results indicate a depressant effect of acute CBZ upon presynaptic 5-HT activity and an increase in presynaptic 5-HT function when CBZ is given for 14 days. Post-synaptic 5-HT function was, however, not altered by CBZ.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 80 (1990), S. 189-194 
    ISSN: 1435-1463
    Keywords: Nicotine enantiomers ; pain ; spinal analgesia ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spinalized rats received an intrathecal injection of either (−)-nicotine or (+)-nicotine in order to study the stereoselectivity of antinociception. Pain threshold was measured using the tail-flick test. Both stereoisomers had antinociceptive effects, but (−)-nicotine was up to 970 times more potent, depending on test conditions. The antinociceptive action of (−)-nicotine was antagonized by mecamylamine and yohimbine but not by naloxone and atropine. The findings show that spinal mechanisms are highly stereoselective toward nicotine, and suggest that primarily nicotinergic andalpha-adrenergic receptors are involved in its central antinociceptive effects.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 65 (1986), S. 135-145 
    ISSN: 1435-1463
    Keywords: Tranylcypromine enantiomers ; monoamine uptake ; monoamine release ; dopamine ; noradrenaline ; serotonin ; synaptosome ; imipramine binding ; blood platelet ; stereoselectivity ; rat ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Studies were carried outin vitro to determine effects of tranylcypromine enantiomers ([+]- and [−]-TCP) on uptake and release of 5-HT, DA and NA in rat synaptosomes and on imipramine binding to rabbit platelets. (+)-TCP was more potent than (−)-TCP as inhibitor of 5-HT uptake and imipramine binding, whereas (−)-TCP was more potent than (+)-TCP as inhibitor of DA and NA uptake. The enantiomers differed only slightly in their effects on monoamine release. The findings agree with previous reports on the stereoselectivity of monoaminergic mechanisms toward TCP enantiomers, and support the notion that the 5-HT uptake site may be associated with the imipramine binding site.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1463
    Keywords: Phenylpiperazine ; monoamine uptake ; NA ; DA ; 5-HT ; MAO ; phenylethylamine ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The diastereomers of 3,N,N′-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2R, 3R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2S, 3S)-TPP was least potent. In contrast, the (2S, 3S)- and (2 S, 3R)-diastereomers of TPP were more potent than (2R, 3R)- and (2R, 3S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.
    Type of Medium: Electronic Resource
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