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Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat.

Abstract
Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
AuthorsP Salmi, T Karlsson, S Ahlenius
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 253 Issue 1-2 Pg. 67-73 (Feb 21 1994) ISSN: 0014-2999 [Print] Netherlands
PMID7912199 (Publication Type: Journal Article)
Chemical References
  • Amphetamines
  • Benzazepines
  • Chromans
  • Dopamine Agents
  • Dopamine D2 Receptor Antagonists
  • Ergolines
  • Receptors, Dopamine D1
  • Salicylamides
  • Serotonin Antagonists
  • Quinpirole
  • Raclopride
  • Oxotremorine
  • A 68930
  • Clozapine
  • Clonidine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
Topics
  • Amphetamines (antagonists & inhibitors)
  • Animals
  • Benzazepines (administration & dosage, pharmacology)
  • Body Temperature (drug effects)
  • Body Temperature Regulation
  • Chromans (pharmacology)
  • Clonidine (pharmacology)
  • Clozapine (antagonists & inhibitors, pharmacology)
  • Dopamine Agents (pharmacology)
  • Dopamine D2 Receptor Antagonists
  • Ergolines (pharmacology)
  • Hypothermia (chemically induced)
  • Injections, Subcutaneous
  • Male
  • Oxotremorine (pharmacology)
  • Quinpirole
  • Raclopride
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 (antagonists & inhibitors, drug effects)
  • Salicylamides (pharmacology)
  • Serotonin Antagonists

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