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  • Electronic Resource  (3)
  • pharmacokinetics  (2)
  • Nociception  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 113 (1997), S. 81-87 
    ISSN: 1432-1106
    Keywords: Serotonin ; Nociception ; Spinal cord ; Pain tests ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of serotonin (5-HT) in the modulation of nociceptive impulse in the spinal cord has been widely studied. However, its activity, considering the nature of noxious stimuli and the type of 5-HT receptors involved, merits to be further elucidated. The present behavioural study was performed to compare the doseantinociceptive effect relationship of 5-HT in rats, after intrathecal, (i.t.) injection (10 μl/rat), using mechanical (paw pressure), thermal (tail immersion and tail-flick) and chemical (formalin) pain tests. In rats submitted to the paw pressure test, 5-HT was found to possess a dose-dependent antinociceptive activity (0.01, 0.1, 1, 10 and 20 μg/rat) when vocalization threshold was assessed as a pain parameter. A peak effect occurred 5 min after the injection and the effect was maintained for 45 min. The lowest active dose was 0.1 μg (maximum increase in vocalization thresholds, 23±3%) and a plateau was observed for 10 μg and 20 μg (maximum increase in vocalization thresholds, 72±7% and 71±6%, respectively). When paw withdrawal was assessed, 5-HT induced a weak hyperalgesic effect for the highest dose (60μg), while other doses were ineffective. In the tail-immersion (warmth and cold) and tail-flick tests, different doses (0.01, 0.1, 1, 10, 30, 60 and 100 μg/rat), were studied. In the two immersion tests, only the highest doses (60 μg and 100 μg) significantly increased the withdrawal thresholds from 5 to 45 min after the injection. The maximum effect was observed at 5 min (23±4% and 21±6% for 60 μg; 27±3%, and 30±6% for 100 μg in the warmth and cold immersion test, respectively). In the tail-flick test, the doses of 30, 60 and 100 μg/rat dose-dependently and significantly increased the withdrawal thresholds from 5 to 45 min after the injection, with a maximum effect at 5 min (30±5% for 30 μg; 37±6% for 60 μg; and 45±4% for 100 μg). In the formalin test, 5-HT (10, 25, 50, 75 and 100 μg/rat) produced dose-related antinociception. The nociceptive response (licking of the injected paw) was significantly reduced from 25 μg (−59±11%) in the early phase, whereas the lowest active dose in the late phase was 50 μg (−46±17%). For both phases, a total inhibition was obtained with 100 μg. It is concluded that the effect of 5-HT on pain tests may differ according to the applied stimulus and the parameter assessed; unspecific effects of 5-HT may modify motor reactions to noxious stimuli. Mechanical test (assessment of vocalization) was the most sensitive to 5-HT. These observations are of importance in order to further study the pharmacological mechanisms involved in 5-HT spinally induced antinociception.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; Apomorphine ; pharmacokinetics ; adverse effect ; on-off effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with Parkinson's disease were given a single sublingual dose of apomorphine in 3 mg tablets (2 patients received 18 mg and 3 patients took 39 mg). The therapeutic effect appeared within 33.0 min and lasted 137 min. There was a significant correlation between peak concentration, area under the curve, dose (mg/kg) and the duration of the therapeutic effect.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: cimotaxone ; MAO inhibitor ; plasma prolactin ; circadian rhythm ; healthy volunteers ; hypothalamic MAO ; prolactin secretion ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prolactin (PRL) secretion is stimulated by serotonin (5-HT) and inhibited by dopamine (DA). 5-HT is generally recognized as a substrate for type A monoamine oxidase (MAO), whereas DA is considered as a substrate for either A or B, or both forms of MAO, depending on the species and tissues used. The effect of cimoxatone, a reversible, selective MAO-A inhibitor, on diurnal variation in plasma PRL level was investigated in healthy adults after a single 40 mg oral dose, as an indirect approach to investigating whether DA is preferentially a substrate for Type A or B MAO in man. The circadian rhythm in PRL, stress conditions and diet were taken into account in the present study, which was placebo-controlled. There was a slight but significant reduction in circulating PRL in the six subjects, which persisted for at least 9 h after cimoxatone. However, the duration of the decrease in plasma PRL was shorter than the inhibition of MAO-A. The results are not inconsistent with the presence of both forms of MAO in the human hypothalamus and with DA as a substrate for both forms in this region, if it is assumed that the hypothalamic concentrations of the drug during the period 0–9 hours was sufficiently high to inhibit DA deamination by both forms of MAO.
    Type of Medium: Electronic Resource
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