Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species.
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PMID:Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets. 135 Sep 96

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.
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PMID:Partial dopamine agonist therapy of levodopa-induced dyskinesias. 810 26

The effects of the partial dopamine agonist terguride (9,10 transdihydrolisuride; THDL) on striatal dopamine receptors were studied by its i.v. administration to 13 patients with Parkinson's disease. Patients were maintained in a steadily mobile state with abnormal involuntary movements by a constant i.v. infusion of levodopa. Terguride showed dopamine antagonist properties in nine patients. In two of these nine patients, a decrease in dyskinesia score was observed without a concomitant worsening of parkinsonian symptoms, whereas in the remaining seven, full parkinsonian akinesia followed THDL administration. The subsequent i.v. injection of the dopamine agonist lisuride reversed THDL-induced akinesia in these seven patients. In the remaining four patients, no clinically significant motor effects were observed. These results show dopamine antagonist activity of terguride in patients with Parkinson's disease treated with Levodopa. Further studies using a wider dose titration are required to evaluate the possible role of dopamine partial agonists in the therapy of levodopa-induced dyskinesias.
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PMID:Antagonist effect of terguride in Parkinson's disease. 168 13

Terguride, an analogue of lisuride, decreased locomotor activity, produced cataplexy, and blocked apomorphine-induced stereotypic behavior. It did not induce stereotypies in rodents or emesis in dogs. However, in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra, terguride produced contralateral rotation. Terguride bound to D-2 striatal dopamine receptors. Terguride has both agonist and antagonist actions at striatal dopamine receptors, but chronic administration did not produce behavioral supersensitivity. These pharmacologic properties differ from those of other antiparkinsonian agents; terguride may be effective for the chronic treatment of Parkinson's disease.
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PMID:Terguride, a mixed dopamine agonist-antagonist, in animal models of Parkinson's disease. 356 89

Terguride, a mixed agonist-antagonist of central dopamine receptors, was administered to eight patients with Parkinson's Disease. The clinical symptomatology of all patients improved significantly. The maximum neurological effect of terguride was noted at the highest daily dose (1.2 mg) after 21 days of treatment in all subjects, with a statistically significant average of 50.6% neurological improvement on the Webster scale in respect to admission. All single scores of the Webster scale decreased significantly: swing of the arms, facial expression, bradikinesia, rigidity and gait, particularly. No significant adverse reactions were observed during treatment. Our study in drug-free parkinsonian patients demonstrated that terguride is able to improve the neurological symptoms similar to DA agonists, but without their typical side effects.
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PMID:Therapeutic efficacy of a partial dopamine agonist in drug-free parkinsonian patients. 407 66

The optimal combination of a dopamine D2 agonist and a D1 agonist was evaluated for symptomatic treatment of Parkinson's disease. Behavioral effects of combination treatment of the full D2 agonist quinpirole or the partial D2 agonist terguride with the full D1 agonist SKF 82958 [(I) 6-Chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetra-hydro-1H-3-benzazepine] were investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity such as irritability, excitability and aggressiveness and of dyskinesias such as licking of paws, chewing and biting. Both quinpirole and SKF 82958 alone improved the parkinsonism with a slight induction of the hyperactivity and dyskinesias. Terguride also improved the parkinsonism but did not induce the hyperactivity and dyskinesias. Combination treatment of quinpirole with SKF 82958 not only showed a tendency to augment the antiparkinsonian effects but also induced the marked hyperactivity and dyskinesias. On the other hand, combination treatment of terguride with SKF 82958 also augmented the antiparkinsonian effects but did not induce any hyperactivity and dyskinesias. These findings suggest that combination therapy with a partial D2 agonist and a full D1 agonist or monotherapy with a dopamine agonist that has both partial D2 and full D1 agonist properties might be beneficial for treating motor dysfunction in Parkinson's disease without inducing dopaminergic side effects.
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PMID:Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF 82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys. 771 82

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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PMID:Terguride in fluctuating parkinsonian patients: a double-blind study versus placebo. 790 60

Behavioral effects of terguride, a partial dopamine D2 agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys were compared with those of the dopamine agonist apomorphine and the dopamine antagonist haloperidol. Terguride alone ameliorated the parkinsonism without inducing any sign of excitability, irritability, or aggressiveness (hyperactivity). Apomorphine alone also ameliorated the parkinsonism but induced marked hyperactivity. Haloperidol alone caused worsening of the parkinsonism, inducing transient eyelid closure. In combination with apomorphine, terguride suppressed the hyperactivity induced by apomorphine without reducing its antiparkinsonian effects. Pretreatment with haloperidol suppressed both the antiparkinsonian effects and the hyperactivity induced by apomorphine. Terguride thus exhibits both antiparkinsonian and antihyperactivity effects in a monkey model of Parkinson's disease, suggesting that terguride might be beneficial for treating motor dysfunction and dopaminergic psychosis in advanced Parkinson's disease.
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PMID:Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. 809 31

Terguride (TER) (2 mg/day) was compared with a placebo in 41 stable Parkinson's disease (PD) patients, so as to test its efficacy as an add-on treatment to spare levodopa (LD). After the 4th week of add-on treatment, LD was reduced by about 25%. The number of "stable" patients (--those with an increase of no more than 20% of the basal Columbia University Rating Scale (CURS) score--remaining after LD reduction was used to compare the two add-on treatments. Most patients, remained "stable" in spite of LD reduction, and no significant differences between the therapies were discovered; the CURS score decreased over time only in the TER group. Hence, TER was shown to be a drug that has DA-ergic properties but with minimal antiparkinsonian efficacy.
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PMID:Terguride in stable Parkinson's disease. 855 16