ergoline and Dystonia

To assess the efficacy and safety of high-dose (up to 20 mg/day) cabergoline in Parkinson's disease (PD) patients with motor fluctuations and/or dyskinesias.. Thirty-four PD patients had cabergoline up-titrated and their levodopa (L-dopa) reduced over a maximum of 20 weeks, followed by at least 6 weeks steady cabergoline dosing. Primary endpoint was change in mean hyperkinesia intensity at the final visit (week 26).. Mean (+/- SD) cabergoline was increased from 6.43 +/- 2.66 to 12.78 +/- 5.67 mg/day and mean L-dopa reduced from 606.6 +/- 263.9 to 370.6 +/- 192.5 mg/day. A significant reduction (P < 0.001) in mean hyperkinesia intensity occurred from baseline (day 0) to week 26. Improvements in 'on with dyskinesias', mean dystonia intensity (P < 0.05), time spent in 'severe off' condition, severity of 'off' periods as well as clinical/patient global impression, and health-related quality of life were observed. Twenty-four drug-related adverse events were recorded of which four were regarded as serious.. High-dose cabergoline was well tolerated and provided significant improvements in the Parkinson symptomatology and a reduced requirement for L-dopa.

Topics: Adolescent; Adult; Aged; Amantadine; Antiparkinson Agents; Cabergoline; Catechols; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Humans; Levodopa; Middle Aged; Nitriles; Parkinson Disease; Piperidines; Prospective Studies; Quality of Life; Selegiline; Severity of Illness Index; Treatment Outcome

Topics: Adult; Aged; Clinical Trials as Topic; Dopamine; Double-Blind Method; Dystonia; Ergolines; Female; Hallucinations; Humans; Lisuride; Male; Middle Aged; Nausea; Paranoid Disorders

Lisuride hydrogen maleate, 0.4 to 5 (mean, 3) mg/d, was given orally to 42 subjects with various types of dystonia. In seven of the eight patients who improved (one with segmental dystonia, one with myoclonic dystonia, two with spasmodic torticollis, two with cranial dystonia, and two with tardive dystonia), the response was confirmed by double-blind placebo substitution. No patients with a suspected structural brain lesion improved. There was no consistent pattern of response among those patients with different forms of idiopathic (primary) dystonia. Lisuride improved some patients, but had no effect on other, apparently identical, patients.

Topics: Administration, Oral; Adult; Age Factors; Aged; Clinical Trials as Topic; Double-Blind Method; Dystonia; Dystonia Musculorum Deformans; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Torticollis

Nine patients with various focal dystonias participated in a 12-week, double-blind, crossover comparison of the dopamine agonist, lisuride, and placebo. Lisuride produced mild objective and subjective improvement in six subjects, but the improvement was not sustained with continued therapy. Because the patients generally identified the active drug by side effects, biasing the study toward finding an effect, and because the benefits were mild and transient, we conclude that lisuride is of limited use in the treatment of focal dystonias.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Dystonia; Ergolines; Female; Hallucinations; Humans; Lisuride; Male; Middle Aged; Nausea; Random Allocation

Topics: Adolescent; Adult; Clinical Trials as Topic; Double-Blind Method; Dystonia; Ergolines; Humans; Lisuride; Middle Aged; Spasm; Torticollis

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.

Topics: Administration, Oral; Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Benzothiazoles; Cebus; Disease Models, Animal; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Female; Haloperidol; Lisuride; Male; Piperidines; Pramipexole; Quinpirole; Raclopride; Salicylamides; Thiazoles

The effects of dopamine D1 and D2 receptor agonists and antagonists were studied in eight Cebus apella monkeys previously treated with haloperidol for two years. SKF 81297 (specific D1 receptor agonist) induced oral hyperkinesia of variable intensity (P less than 0.01): some of the monkeys developed extreme lip smacking, tonque protrusions and licking movements while others developed only slight lip movements. A combined treatment of SKF 81297 with LY 171555 (full D2 receptor agonist) or SCH 23390 (D1 receptor antagonist) inhibited the oral hyperkinesia induced by SKF 81297 (P less than 0.01, P less than 0.02, respectively). Raclopride (D2 receptor antagonist) did not statistically change oral hyperkinesia (P less than 0.2), although five monkeys showed increased oral movements; most of these monkeys had pre-existing hyperkinesia. Treatment with SCH 23390 or raclopride resulted in an identical dystonic/cataleptic syndrome. SKF 81297 inhibited the dystonia induced by SCH 23390, while it did not significantly affect raclopride dystonia. The investigation indicates that oral dyskinesia may be related to an imbalance in D1 receptor and D2 receptor stimulation in favor of D1 receptors. The question now is whether D1 receptor antagonists, which may have antipsychotic potential, will produce tardive dyskinesia after long-term use.

Topics: Animals; Antipsychotic Agents; Benzazepines; Blinking; Cebus; Dopamine Agents; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Female; Grooming; Hypnotics and Sedatives; Male; Quinpirole; Raclopride; Receptors, Dopamine; Salicylamides; Substance Withdrawal Syndrome

Meige's disease is a distressing complaint, the treatment of which often poses a challenge to the neurologist. The patient described here had blepharospasm-oromandibular dystonia, which responded transiently to oral lisuride. On three occasions, drug holidays successfully restored efficacy but thereafter further trials proved fruitless. Continuous subcutaneous lisuride administration in 0.35 mg doses per day, by means of a portable infusion pump, led to sustained improvement for 7 months. No major side effects were observed. Our findings suggest that this treatment deserves further trials.

Topics: Domperidone; Dystonia; Ergolines; Female; Humans; Injections, Subcutaneous; Lisuride; Meige Syndrome; Middle Aged

Selective D1 and D2 dopamine (DA) antagonists and agonists were given to 4 Cebus monkeys who had previously received haloperidol treatment for 4 years. SCH 23390 (a selective D1 antagonist) and raclopride (a selective D2 antagonist) induced identical syndromes consisting of dystonia and oral dyskinesia. Biperiden (an anticholinergic drug) and LY 171555 (a selective D2 agonist) completely antagonized the dystonia and dyskinesia induced by SCH 23390 as well as raclopride. The combined treatment with LY 171555 and SCH 23390 (but not LY 171555 and raclopride) caused pronounced sedation. LY 171555 induced repetitive movements of head, legs and trunk, but no oral dyskinesia. SKF 38393 (a partial D1 agonist) caused slight sedation, minimal oral dyskinesia and a significant reduction in D2 agonist-induced repetitive movements.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Antipsychotic Agents; Benzazepines; Biperiden; Cebus; Dystonia; Ergolines; Haloperidol; Male; Movement Disorders; Quinpirole; Raclopride; Receptors, Dopamine; Salicylamides; Stereotyped Behavior

Eleven patients who presented with predystonic syndrome later developed pure dystonic syndromes and later developed parkinsonism. This suggests that dystonic syndromes can be the precursor to a mixed syndrome including both dystonia and parkinsonism. While the parkinsonian features in such patients respond to either levodopa or direct-acting agonists, levodopa often exacerbates the underlying dystonia. Direct acting agonists appear to be less liable to do this.

Topics: Adult; Bromocriptine; Carbidopa; Dystonia; Ergolines; Humans; Levodopa; Meige Syndrome; Middle Aged; Parkinson Disease; Pergolide; Torticollis

We used pergolide to treat 10 patients with idiopathic Parkinson's disease who had first responded to, and then failed, bromocriptine therapy. At the end of 5 years, patients had improved when compared with study entry. Peak efficacy, equal with both drugs, was seen at 12 months. After a mean treatment of 29 months, bromocriptine was no longer effective, but pergolide was still beneficial.

Topics: Aged; Antiparkinson Agents; Bromocriptine; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Female; Hallucinations; Humans; Levodopa; Male; Middle Aged; Nausea; Outcome and Process Assessment, Health Care; Parkinson Disease; Pergolide; Time Factors

Topics: Bromocriptine; Dystonia; Ergolines; Humans; Lisuride

Topics: Animals; Basal Ganglia Diseases; Chorea; Corpus Striatum; Dystonia; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Parkinson Disease; Rats; Syndrome; Torticollis

In this study the effects of an acute injection of lisuride and apomorphine in 12 subjects affected by dystonic-dyskinetic syndromes of different aetiology are evaluated: 3 patients with spasmodic torticollis, 4 with tardive dyskinesia and 5 Parkinson patients suffering from "on-off" attacks with prominent dyskinesias during the mobile phase. In the last group drugs were administered during the "on" phase. In 11 out of 12 patients both lisuride and apomorphine induced a marked improvement of the abnormal involuntary movements. In Parkinson and torticollis patients both drugs also reduced the rigidity. In comparison to apomorphine, lisuride showed a more effective and long-lasting action. Only in one Parkinson patient did the drugs fail in showing any change.

Topics: Apomorphine; Dystonia; Ergolines; Evaluation Studies as Topic; Female; Humans; Lisuride; Male; Middle Aged; Movement Disorders

Topics: Aged; Carbidopa; Dystonia; Ergolines; Female; Hepatolenticular Degeneration; Humans; Huntington Disease; Levodopa; Male; Middle Aged; Movement Disorders; Parkinson Disease