Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist

Pharmacol Biochem Behav. 1991 Jan;38(1):147-54. doi: 10.1016/0091-3057(91)90603-y.

Abstract

These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a Ki for D2 receptors of 2.9 x 10(-8) M with no affinity for D1 at 10(-4) M in the rat. Ropinirole was weakly active at alpha 2-adrenoceptors and 5-HT2 receptors but inactive at 5-HT1, benzodiazepine and gamma-aminobutyric acid receptors or alpha 1 and beta-adrenoceptors. In rodents, ropinirole, like apomorphine, caused biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice with no tolerance to the latter after 14 days treatment. Amphetamine caused ipsilateral responses in the lesioned mice. Ropinirole did not cause marked stereotypies. In marmosets ropinirole (0.05-1.0 mg/kg SC or 0.1 mg/kg PO) reversed all motor and behavioural deficits induced by MPTP. This response started 10-20 minutes after dosing, and exceeded 2 hours. No tolerance was seen following chronic b.i.d. treatment. Similar results were obtained with 1-dopa plus benserazide; however, 1-dopa always caused emesis, whereas beneficial effects were shown with ropinirole in the absence of this side effect. These results support the continued clinical assessment of ropinirole for the treatment of Parkinson's disease.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Adenylyl Cyclases / metabolism
  • Animals
  • Antiparkinson Agents
  • Blood Platelets / metabolism
  • Callitrichinae
  • Cattle
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / enzymology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dopamine Agents / pharmacology*
  • Female
  • Humans
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / physiopathology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Dopamine / metabolism
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, Serotonin / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Antiparkinson Agents
  • Dopamine Agents
  • Indoles
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Receptors, Dopamine
  • Receptors, GABA-A
  • Receptors, Serotonin
  • ropinirole
  • gamma-Aminobutyric Acid
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Adenylyl Cyclases