5-HT(2C) receptor antagonists enhance the behavioural response to dopamine D(1) receptor agonists in the 6-hydroxydopamine-lesioned rat.

Abstract

Non-dopaminergic therapies are of potential interest in the treatment of Parkinson's disease given the complications associated with current dopamine-replacement therapies. In this study we demonstrate that SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3, 5-tetrahydropyrrol[2,3-f]indole) (20 mg/kg) enhanced the actions of the dopamine D(1) receptor agonist, SKF 82958 ((+)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide) (1 mg/kg), in eliciting locomotion in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. This action was only seen following prior priming with L-DOPA (L-3, 4-dihydroxyphenylalanine). SB 206553 had no effect on rotational behaviour when given alone. 5-HT(2C) receptor antagonists may have potential as a means of reducing reliance on dopamine replacement in the treatment of Parkinson's disease.

• Authors: S H Fox, J M Brotchie
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 398 Issue 1 Pg. 59-64 (Jun 09 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10856448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Benzazepines
• Dopamine Agonists
• Indoles
• Pyridines
• Receptor, Serotonin, 5-HT2C
• Receptors, Dopamine D1
• Receptors, Serotonin
• Serotonin Antagonists
• Levodopa
• SK&F 82958
• Oxidopamine
• SB 206553

Topics

• Animals
• Antiparkinson Agents (pharmacology)
• Behavior, Animal (drug effects)
• Benzazepines (pharmacology)
• Disease Models, Animal
• Dopamine Agonists (pharmacology)
• Indoles (pharmacology)
• Levodopa (pharmacology)
• Locomotion (drug effects)
• Male
• Oxidopamine (adverse effects)
• Parkinson Disease, Secondary (chemically induced, drug therapy, physiopathology)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT2C
• Receptors, Dopamine D1 (agonists)
• Receptors, Serotonin (drug effects)
• Serotonin Antagonists (pharmacology)