Terguride in Parkinsonism a multicenter trial

Filipová, M; Filip, V; Macek, Z; Müllerová, S; Marková, Jolana; Kás, S; B, Zizková; Krivka, J; Votavová, M; Krejcová, H

doi:10.1007/bf00450549

Cited by 15 publications

(2 citation statements)

References 8 publications

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“…Although terguride showed weak partial agonist activity in hD 2L receptor-expressing SH-SY5Y cells, its efficacy was much lower than that of quinpirole (Gilliland and Alper, 2000). Furthermore, although terguride showed modest antiparkinson activity and attenuated L-DOPA-induced dyskinesia in primates, it was effective in only a small percentage (10 -20%) of Parkinson's disease patients in (subsequently discontinued) clinical trials (Filipova et al, 1988;Akai et al, 1993). Furthermore, roxindole, which likewise exhibited low efficacy at hD 2L and hD 2S receptors (NewmanTancredi et al, 1999a), failed to reduce L-DOPA-induced dyskinesias in Parkinson's disease patients and has not, as yet, been shown to possess antiparkinson activity in human.…”

Section: Discussionmentioning

confidence: 99%

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor

Newman‐Tancredi¹,

Cussac²,

Audinot³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

171

133

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The accompanying multivariate analysis of the binding profiles of antiparkinson agents revealed contrasting patterns of affinities at diverse classes of monoaminergic receptor. Herein, we characterized efficacies at human (h)D 2SHORT(S) , hD 2LONG(L) , hD 3 , and hD 4.4 receptors and at h␣ 2A -, h␣ 2B -, h␣ 2C -, and h␣ 1A -adrenoceptors (ARs). As determined by guanosine 5Ј-O-(3-[ S]GTP␥S) binding, no ligand displayed "full" efficacy relative to dopamine (100%) at all "D 2 -like" sites. However, at hD 2S receptors quinpirole, pramipexole, ropinirole, quinerolane, pergolide, and cabergoline were as efficacious as dopamine (E maxՆ 100%); TL99, talipexole, and apomorphine were highly efficacious (79 -92%); piribedil, lisuride, bromocriptine, and terguride showed intermediate efficacy (40 -55%); and roxindole displayed low efficacy (11%). For all drugs, efficacies were lower at hD 2L receptors, with terguride and roxindole acting as antagonists. At hD 3 receptors, efficacies ranged from 33% (roxindole) to 94% (TL99), whereas, for hD 4 receptors, highest efficacies (ϳ70%) were seen for quinerolane, quinpirole, and TL99, whereas piribedil and terguride behaved as antagonists and bromocriptine was inactive. Although efficacies at hD 2S versus hD 2L sites were highly correlated (r ϭ 0.79), they correlated only modestly to hD 3 /hD 4 sites (r ϭ 0.44 -0.59). In [ 35 S]GTP␥S studies of h␣ 2A -ARs, TL99 (108%), pramipexole (52%), talipexole (51%), pergolide (31%), apomorphine (16%), and quinerolane (11%) were agonists and ropinirole and roxindole were inactive, whereas piribedil and other agents were antagonists. Similar findings were obtained at h␣ 2B -and h␣ 2C -ARs. Using (Wang et al., 2000). As shown in the accompanying article , therapeutically used antiparkinson agents recognize D 2S and D 2L isoforms with similar affinity, and many antiparkinson agents also interact with dopamine D 3 receptors. Although the density of striatal D 3 receptors is reduced upon degeneration of nigrostriatal dopaminergic pathways, exposure to L-DOPA may induce their up-regulation, reflecting complex regulatory mechanisms involving dopamine D 1 receptors and brainderived neurotrophic factor (Quik et al., 2000;Guillin et al., 2001;Joyce, 2001). Nevertheless, the precise nature of functional interrelationships among D 3 , D 2 , and D 1 receptors, and the implication of D 3 receptors in the therapeutic comArticle, publication date, and citation information can be found at

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Section: Discussionmentioning

confidence: 99%

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor

Newman‐Tancredi¹,

Cussac²,

Audinot³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

171

133

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“…Spiral drawing as assessment of tremor is recommended by the Movement Disorder Society 1. It is also used in the assessment of akinesia in Parkinson's disease (PD),2 tremor in multiple sclerosis,3 and essential tremor,4–9 as well as for evaluating the therapeutic effect of deep brain stimulation 10. In each of these cited works, all spirals are assessed by visual evaluation.…”

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confidence: 99%

Spiralometry: Computerized assessment of tremor amplitude on the basis of spiral drawing

Kraus

Hoffmann

2010

Movement Disorders

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Spiral drawing has been used for the assessment of the impact of therapy on motor performance in various movement disorders (e.g. in Parkinson's disease, especially for tremor and hypokinesia). Nevertheless, there are only few guidelines available providing some kind of standardized interpretation. The published protocol with the highest standard is that of Bain and Findley. Kinetic tremor assessed by spiral drawing is not quantified by alternative approaches so far and is not even considered by most rating scales. However, kinetic tremor is quite common and represents a significant impairment in the everyday life of parkinsonian patients. More complex instrumental methods for the quantification of kinetic tremor have not been practical as they, e.g., require relatively expensive equipment or have an unfavourable effort/benefit ratio. We pursued an alternative approach, where we scan drawn spirals to a computer-algorithm that calculates the tremor amplitude. Our standardized method can be applied without difficulty in patients needing only paper and pencil. The evaluation is fully automated, and therefore, it is appropriate for the assessment of therapeutic efficacy in very large populations. The objectivity of the approach represents a significant advantage. In the actual paper, we present how we analyzed the original spirals published by Bain and Findley to validate our computerized assessment. We found a highly significant connection between both methods (explained variance: 88.9%).

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Terguride in fluctuating parkinsonian patients: A double‐blind study versus placebo

et al. 1993

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Terguride (TER), a semisynthetic derivative of lisuride, has been found to display dopamine (DA) agonist and DA antagonist effects in animals, depending on the experimental model used. TER (2 mg/day) was compared to placebo in 41 fluctuating Parkinson's disease patients to test its effect on akinesia and dyskinesia. Mean hours "off" decreased at weeks 6 and 12 (p < 0.05) in the TER group but the overall difference from the placebo group was not significant. Only the TER group displayed a decrease over time in mean Columbia University Rating Scale total score "on" and "off" (p = 0.001 and p = 0.03, respectively). Duration of involuntary movements and resulting disability were not significantly different between patients on TER and those on placebo administration. In the overall evaluation, patients preferred TER (p = 0.01). Tolerance of TER was very good in all but one patient whose wearing-off increased; no one dropped out because of side effects. This 3-month double-blind study showed that TER, added to stable doses of L-dopa, may have slight antiparkinsonian efficacy.

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Terguride in Parkinsonism a multicenter trial

Cited by 15 publications

References 8 publications

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor

Spiralometry: Computerized assessment of tremor amplitude on the basis of spiral drawing

Terguride in fluctuating parkinsonian patients: A double‐blind study versus placebo

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