dironyl and Dyskinesia--Drug-Induced

Terguride, a partial dopamine agonist, was administered in a 4-week open clinical trial to 17 schizophrenic patients suffering from extrapyramidal side effects of neuroleptic treatment. The neuroleptic dosage was kept constant. The mean final daily dose of terguride reached 3.4 mg (SD = 2.0). Fourteen patients completed the trial. Total scores on the Rating Scale for Extrapyramidal Side Effects and the Brief Psychiatric Rating Scale showed a significant improvement of 69% and 40%, respectively. There was also a significant improvement in all BPRS factor scores.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Dopamine Agents; Dyskinesia, Drug-Induced; Female; Humans; Lisuride; Male; Middle Aged; Neurologic Examination; Parkinson Disease, Secondary; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

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

We administered the partial dopamine agonist terguride under controlled conditions to patients with Parkinson's disease (PD), both as monotherapy and in conjunction with intravenous levodopa. Terguride produced a dose-dependent decrease in levodopa-induced dyskinesias (up to 53%) in seven patients without concomitant worsening of parkinsonism, and had no significant antiparkinsonian effect when administered alone. Partial dopamine agonists may hold some promise in the adjuvant therapy of patients with advanced PD.

Topics: Adult; Aged; Dopamine Agents; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Levodopa; Lisuride; Middle Aged; Movement

Terguride, a partial DA-agonist with both dopaminergic and antidopaminergic properties, was tested in 11 PD patients in the "decompensated" phase of the disease, characterized by the presence of dyskinesias and motor fluctuations. Combined treatment of these patients with 1 mg/day of terguride and stabilized doses of levodopa reduced the severity and frequency of dyskinesias and motor fluctuations along with a slight but significant improvement of parkinsonian clinical picture. The "modulatory" effect of terguride on DA receptors, in this experimental conditions, is discussed.

Topics: Dyskinesia, Drug-Induced; Humans; Levodopa; Lisuride; Male; Middle Aged; Parkinson Disease