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  • 1
    ISSN: 1432-2072
    Keywords: Scopolamine ; Ondansetron ; m-Chlorophenylpiperazine ; Cognitive pharmacologic modeling ; Geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonistm-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine + ondansetron, and scopolamine + m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: m-Chlorophenylpiperazine ; Ritanserin Spiperone ; Attenuated ; Tolerance ; MDL-72222 Propranolol ; Ketanserin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of various 5-HT receptor subtype-selective antagonists were studied on phenylisopropylamine hallucinogen1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in Wistar rats, in an attempt to characterize the 5-HT receptor subtype mediating DOI-induced hyperthermia. Intraperitoneal administration of DOI to rats produced hyperthermia with a peak effect at 60 min. Pretreatment with propranolol (β-adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate DOI-induced hyperthermia. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist), ketanserin, LY53857, mesulergine, mianserin and ritanserin (5-HT2C/5-HT2A antagonists), as well as spiperone (5-HT1A/5-HT2A/D2 antagonist), significantly attenuated DOI-induced hyperthermia. Furthermore, daily administration of DOI (2.5 mg/kg per day) for 17 days did not produce either tolerance to its hyperthermic effect or modifym-CPP-induced hyperthermia in rats. These findings suggest that DOI-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors.
    Type of Medium: Electronic Resource
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