cqa-206-291 and Parkinson-Disease

CQA 206-291, a mixed D1-D2 receptor agonist that also possesses dualistic dopamine antagonist-agonist properties, was investigated in a double-blind, placebo-controlled trial in individuals with Parkinson's disease of moderate severity. Significant improvement was noted in the treatment groups compared to the placebo group. Adverse effects were generally mild and transient. CQA appears to be an effective, well-tolerated agent in the treatment of Parkinson's disease. Nevertheless, because of laboratory-based toxicity concerns, CQA has been withdrawn from further human study and will not be developed clinically.

Topics: Activities of Daily Living; Aged; Dopamine Agents; Double-Blind Method; Drug Interactions; Ergolines; Humans; Levodopa; Middle Aged; Parkinson Disease

The antiparkinsonian efficacy and tolerability of CQA 206-291, a novel ergoline derivative with potent dopamine agonist properties, were studied during 2 months of treatment in 72 parkinsonian patients. In 36 de novo patients (patients who have not previously been treated with levodopa or dopamine agonists), CQA 206-291 was studied in an open design, while in 36 levodopa-treated patients, CQA 206-291 was studied in a randomized, double-blind, parallel-group, placebo-controlled design. CQA 206-291 induced in both groups a significant antiparkinsonian effect with an effective dose range of 5-30 mg/day. The spectrum of adverse events was similar to what is commonly observed with dopamine agonists. Further studies are required to assess the putative therapeutic advantages of CQA 206-291 when compared to other antiparkinsonian drugs.

Topics: Aged; Antiparkinson Agents; Drug Therapy, Combination; Ergolines; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease

CQA 206-291, a new ergot derivative with a "biphasic" dopaminergic profile, was studied in 6 patients with longstanding Parkinson's disease suffering from pronounced fluctuations in hourly mobility. On alternate days, up to seven single doses, escalating from 0.2 to 20 mg, were given as replacement for the usual first morning dose of levodopa. At the most effective dosage, four of the six patients obtained as good a peak response to CQA (8-20 mg) as to L-dopa. Side effects were common and similar to other ergot derivatives, suggesting that the initial weak dopamine antagonist properties of the parent compound, documented in animals, may be of little clinical significance. However, comparative studies will be needed to confirm this suspicion. The addition of domperidone successfully reduced the incidence and severity of side effects. CQA 206-291 has potent anti-parkinsonian properties; further longer-term treatment trials are indicated.

Topics: Aged; Antiparkinson Agents; Ergolines; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Psychomotor Performance

CQA 206-291, a new D2 dopamine receptor agonist with a biphasic dopaminergic profile, was given to six patients with idiopathic Parkinson's disease after overnight drug withdrawal. With incremental single oral doses of CQA, a dose-related, clinically significant, and prolonged antiparkinsonian effect was observed. Most subjects experienced drowsiness after the drug while a minority of subjects experienced nausea and/or vomiting or postural hypotension. Further study of this drug in humans is indicated.

Topics: Aged; Dopamine Agents; Dose-Response Relationship, Drug; Drug Evaluation; Ergolines; Female; Humans; Male; Middle Aged; Movement; Parkinson Disease; Receptors, Dopamine