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

doi:10.1016/0091-3057(91)90603-Y

Pharmacology Biochemistry and Behavior

Volume 38, Issue 1, January 1991, Pages 147-154

https://doi.org/10.1016/0091-3057(91)90603-Y Get rights and content

Abstract

These studies characterise the pharmacology of ropinirole, a selective D-2 agonist. High-affinity human caudate binding revealed a K_i for D₂ receptors of 2.9 × 10⁻⁸ M with no affinity for D₁ at 10⁻⁴ M in the rat. Ropinirole was weakly active at α₂-adrenoceptors and 5-HT₂ receptors but inactive at 5-HT₁, benzodiazepine and gamma-aminobu acid receptors or α₁ and β-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 OPO) reversed all motor and behavioral 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.

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¹: Present address: Toxicol Laboratories, Ledbury, Herefordshire, HR8 1LH.

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

Abstract

Characterization of the binding of [3H] SCH 23390, a selective D-1 receptor antagonist

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

Eur. J. Pharmacol.

Lancet

Lancet

Biochem. Pharmacol.

Lancet

Lancet

Pharmacol. Ther.

Serotonin and lysergic acid diethyline binding in rat brain membranes: relationship to postsynaptic serotonin receptors

Mol. Pharmacol.

A model of nausea and emesis in the common marmoset

Br. J. Pharmacol.

Effects of chronic oral administration of antidepressants, desmethylimiframine and zimelidine on rat cortical GABAB binding sites: a comparison with 5-HT2 binding site changes

Br. J. Pharmacol.

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

Characterization of the binding of [³H] SCH 23390, a selective D-1 receptor antagonist

Effects of chronic oral administration of antidepressants, desmethylimiframine and zimelidine on rat cortical GABA_B binding sites: a comparison with 5-HT₂ binding site changes