Dopamine Receptor Subtypes as Targets for the Pharmacotherapy of Parkinson's Disease (original) (raw)

Advances in Pharmacology, 1997

Abstract

ABSTRACT Long-term treatment of Parkinson's disease (PD) patients with L-dopa and/or D2-receptor agonists leads to wearing off, on-off effects, and/or dyskinesias. Apart from D2 receptors, D1 receptors also might serve as pharmacotherapeutic targets in PD because D1 receptors also are targets for the action of DA in the striatum and are involved in the regulation of motor behavior. The researchers have elaborated in this issue by testing two newly developed benzazepines in the primate MPTP model for PD. They have focused on the therapeutic and unwanted side effects of the two D1 agonists SKF 81297 and SKF 82958. It is found that SKF 81297 apparently “stimulates” motor behavior, the effects are predominantly dyskinetic, abnormal, and clearly not goal directed. Thus, it cannot be considered as “real” antiparkinsonian. The experiment in bilaterally MPTP-lesioned rhesus monkeys to investigate the effects of a D1 agonist and especially the behavioral effects of chronic treatment shows that the D1 agonists SKF 81297 and SKF 82958 “stimulate” to a certain extent motor behavior. But they lack a clear effect on goal-directed movements that might be considered a real antiparkinsonian effect. However, both agonists clearly induce dyskinetic effects and epileptoid activity. Moreover, it has been reported that the effects of several benzazepines on motor behavior have failed to correlate with their efficacy in stimulating adenylate cyclase activity, a paradigm generally considered the hallmark of D1-receptor efficacy.

benjamin drukarch hasn't uploaded this paper.

Let benjamin know you want this paper to be uploaded.

Ask for this paper to be uploaded.