Clozapine antagonism of D-1 and D-2 dopamine receptor-mediated behaviors.

Abstract

When tested in rats supersensitive to dopamine agonists, the atypical neuroleptic clozapine displayed pharmacological properties expected of both a D-1 and D-2 receptor antagonist. The locomotor response induced by the D-1 receptor agonist SKF-38393 in neonatal-6-hydroxydopamine (6-OHDA)-lesioned rats was reversed in a dose-related fashion, although a complete blockade of this behavior was not observed indicative for only a partial antagonism of D-1 receptor function. Clozapine also blocked the self mutilation resulting from L-dihydroxyphenylalanine (L-DOPA) administration to neonatal-6-OHDA-lesioned rats, an effect previously linked to D-1 receptor activation. At higher doses, clozapine blocked the locomotor activity elicited by the D-2 agonist LY-171555 in adult-6-OHDA-lesioned rats. Therefore, the action of clozapine on D-1 as well as D-2 receptor-mediated behaviors contributes to its pharmacological effects. The ability of clozapine to stop self-mutilatory behavior in neonatal-6-OHDA-lesioned rats suggests that this drug might be an effective treatment for self-injurious behavior associated with the Lesch-Nyhan syndrome and mental retardation.

• Authors: H E Criswell, R A Mueller, G A Breese
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 159 Issue 2 Pg. 141-7 (Jan 10 1989) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2495973 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Appetite Depressants
• Benzazepines
• Dibenzazepines
• Ergolines
• Hydroxydopamines
• Receptors, Cholinergic
• Receptors, Dopamine
• Receptors, Serotonin
• Quinpirole
• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• Oxidopamine
• Clozapine

Topics

• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• Animals
• Animals, Newborn (physiology)
• Appetite Depressants (pharmacology)
• Behavior, Animal (drug effects)
• Benzazepines (pharmacology)
• Clozapine (pharmacology)
• Dibenzazepines (pharmacology)
• Ergolines (pharmacology)
• Female
• Hydroxydopamines (pharmacology)
• Motor Activity (drug effects)
• Oxidopamine
• Pregnancy
• Quinpirole
• Rats
• Rats, Inbred Strains
• Receptors, Cholinergic (drug effects)
• Receptors, Dopamine (drug effects)
• Receptors, Serotonin (drug effects)