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

Eur J Pharmacol. 2000 Jun 9;398(1):59-64. doi: 10.1016/s0014-2999(00)00238-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Parkinson Disease, Secondary / drug therapy
  • Parkinson Disease, Secondary / physiopathology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / pharmacology*

Substances

  • 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