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Serotonin antagonists and central hyperthermia produced by biogenic amines in conscious rabbits.

Abstract
Previous studies have shown that the hyperthermia produced by intracerebroventricular injection of 5-hydroxytryptamine (5-HT) to conscious rabbits was antagonized by cyproheptadine and increased by LSD. Other putative antagonists, i.e. cinanserin, methiothepin, 2-bromo LSD, methysergide and dimetiotazine are investigated in the present report. Cinanserin and methiothepin resembeld cyproheptadine, 2-bromo LSD had almost the same effects as LSD and methysergide exhibited a mixed pattern of action, being depressant or potentiating as a function of dose. Dimetiotazine had no specific action. Cinanserin, however, differed from cyproheptadine in selectively antagonizing and early component of the 5-HT rise, unmasking an important fall and leaving a late hyperthermic component unaffected, thus disclosing three distinct effects of 5-HT action. The cinanserin, methiothepin and methysergide antagonism of the 5-HT-induced temperature rise was greater than the antagonism of the noradrenaline (NA)-induced rise. Methiothepin and methysergide inhibited both the 5-HT and DA hyperthermia; cinanserin--like cyproheptadine--was more effective on the 5-HT rise. The potentiation of the 5-HT temperature rise by 2-bromo LSD and methysergide was more developed than was the potentiation of the NA and DA rises. The effects of the drugs studied on 5-HT action argue in favour of the existence of several types of central 5-HT receptors. The dissociation observed between the antagonism to 5-HT and that to DA does not favour a mediation of DA hyperthermia by 5-HT; antiserotonin drug antagonism of DA hyperthermia is more simply accounted for by interactions at the level fo specific DA receptors. The potentiation of the 5-HT-induced temperature rise by 2-bromo LSD and methysergide might result from an antagonism of the hypothermic component. As with LSD, 2-bromo LSD and methysergide alone also produced hyperthermia, the origin of which is briefly discussed.
AuthorsJ M Girault, J J Jacob
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 53 Issue 2 Pg. 191-200 (Jan 01 1979) ISSN: 0014-2999 [Print] Netherlands
PMID32059 (Publication Type: Journal Article)
Chemical References
  • Phenothiazines
  • Serotonin Antagonists
  • Serotonin
  • Methiothepin
  • Lysergic Acid Diethylamide
  • Cinanserin
  • Dopamine
  • Norepinephrine
  • Methysergide
Topics
  • Animals
  • Body Temperature (drug effects)
  • Cinanserin (pharmacology)
  • Dopamine (pharmacology)
  • Fever (chemically induced)
  • Lysergic Acid Diethylamide (pharmacology)
  • Male
  • Methiothepin (pharmacology)
  • Methysergide (pharmacology)
  • Norepinephrine (pharmacology)
  • Phenothiazines (pharmacology)
  • Rabbits
  • Serotonin (pharmacology)
  • Serotonin Antagonists (pharmacology)

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