Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen parkinsonian patients, mean age 57 (range 41-71), with a mean 9 year duration of Parkinson's disease, with "on-off" motor fluctuations were treated with pergolide mesylate 1.6 mg/die (range 1-5) for three months. The treatment resulted in an improvement of akinesia, tremor and rigidity, of the severity of phase "off" and of the duration of time "on". No significant improvements were obtained in the severity of dyskinesia. Three patients considered the treatment excellent and capable of restoring their working abilities. The drug was generally well tolerated. Pergolide was discontinued because of orthostatic hypotension in two patients and because of hallucinations in one patient. We consider these results a favorable progress in the treatment of Parkinson's disease.
 ...
PMID:[Pergolide mesylate in the treatment of Parkinson's disease resistant to other treatments. First Italian experience]. 182 72

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.
 ...
PMID:Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. 218 10

The capacity of the ergoline, pergolide, and of the partial ergoline, LY 141865, to stimulate pre- and postsynaptic dopamine (DA) receptors was investigated. Binding studies have revealed that pergolide has a high affinity, while the partial ergoline, LY 141865, has a low affinity for the postsynaptic striatal DA receptors in vitro. Two behavioral animal models were used to assess the DA agonist potencies of these compounds for the postsynaptic DA receptors in vivo. Pergolide induced turning behavior in rats with 6-hydroxydopamine (6-OH-DA) lesions, and relief of tremor in monkeys with ventromedial tegmental lesions, at a lower dose and for a longer duration than LY 141865. An in vivo and an in vitro biochemical test was use to measure the ability of these compounds to stimulate presynaptic DA receptors. In the in vitro test, pergolide and LY 141865 were found to have low inhibitory activity for synaptosomal tyrosine hydroxylase, while in the in vivo test, both drugs were effective even in low doses in reversing the gamma-butyrolactone elicited increased accumulation of striatal DOPA. These results suggest that pergolide has a high affinity for pre- and postsynaptic DA receptors, while its partial ergoline analogue has a high affinity for the presynaptic, but not for the postsynaptic DA receptors. The data also suggest that dopamine synthesis in vitro and in vivo may be regulated by different presynaptic DA receptors.
 ...
PMID:Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by partial ergoline. 611 95

The activity of pergolide, an N-propylergoline derivative, has been tested for stimulation of central dopaminergic receptors. Binding to dopamine receptors shows that pergolide acts as an agonist with respect to these receptors. GTP decreases the potencies of dopamine agonists and of pergolide, but not of bromocriptine, to displace [3H]spiroperidol ([3H]Spi) from striatal membrane sites. The GTP-sensitive site labeled by [3H]Spi seems to be localized on intrastriatal dopamine receptors. The potency of dopamine agonists and of pergolide to displace [3H]Spi from striatal receptor sites is reduced in membranes exposed to higher temperatures. Pergolide, but not hitherto-tested dopaminergic ergots, stimulates dopamine-sensitive adenylate cyclase in striatal homogenates. Thus, pergolide, unlike other dopaminergic ergots, acts as an agonist on GTP-sensitive components of [3H]Spi binding and stimulates dopamine receptors linked to dopamine-sensitive adenylate cyclase. The drug also induces turning behavior in rats with 6-OH-dopamine lesions and relieves tremor in monkeys with ventromedial tegmental lesions for a longer time at a lower dose than other tested dopaminergic ergots. Other studies have shown that it is effective in the treatment of patients with advanced parkinsonism.
 ...
PMID:Interaction of pergolide with central dopaminergic receptors. 693 44

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).
 ...
PMID:Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. 1253 11

We report a 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty in eye-lid opening, and marked pseudo-bulbar palsy. He felt difficulty of it, hand movement at 59 years old. When he was 60 years old, monotonous speech and slowness of movement appeared. He visited a neurologist who noted vertical gaze palsy, neck rigidity, and bradykinesia. He was diagnosed as progressive supranuclear palsy (PSP) and given 300 mg L-Dopa/Benserazide by the neurologist. This medication improved his rigidity and bradykinesia. At 62 years of the age, his eye-lids closed involuntary and it was difficult to open. In addition, he began to complain of wearing-off, autonomic symptoms, and dysphagia. Anti-parkinsonian drugs were increased, but his bradykinesia progressed. At 64 years of the age, he was admitted to the Neurology Service of Juntendo Hospital. On admission, he was alert and not demented. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, upward and downward gaze were markedly restricted. His face was hypomimic and seborrhoic. It was difficult to swallow liquid or solid for him. No weakness was noted, but he walked in small steps with freezing and falling tendency to backward. Rigidity was noted on his extremities and stronger on his left side than right. Tremor was absent. Bradykinesia of his body and extremities was marked. No cerebellar ataxia was noted. Deep tendon reflexes were within normal range. Planter response was flexor bilaterally. Myerson's sign was noted. Sensory and autonomic function were normal. He was treated with L-Dopa, Pergolide, and Bromocriptine. However, these medications improved his bradykinesia and gait disturbance only slightly, dysphagia became progressively worse. He developed aspiration pneumonia when he was 65 years old and admitted to Juntendo Hospital. A large amount of sputum was aspirated from his trachea. Two days after from admission, he was found dead on his bed. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy (PSP). Other differential diagnoses included Parkinson's disease, pallido-nigroluysian atrophy (PNLA), multiple system atrophy (MSA), and corticobasal degeneration(CBD). Many participants considered that PSP or PNLA was most likely. Post-mortem exmination revealed marked nigral neuronal loss and gliosis. The globus pallidus and the luysian body changed mildly. However, the frontal cortex was relatively spared, there were many ballooned neurons in the cortical layer. Other parts were spared. With sliver (Bodian and Gallyas-Braak) and anti-phsphorylated tau stain, abundant astrocytic plaques, neurofibrillary tangles, and argyrophilic threads on the frontal cortex, striatum, and substantia nigra were seen. There was no tufted astrocyte which was hallmark of diagnosis of PSP. In addition, several Lewy bodies were seen in the brainstem. Because astrocyte plaque was considered specific for pathology of CBD, the pathologist revealed that the pathological diagnosis of this patient was CBD. Nevertheless, discussion was focused on the relatively mild degeneration of the frontal cortex for CBD.
 ...
PMID:[A 65-year-old man with rigid-bradykinetic parkinsonism, vertical gaze palsy, difficulty of eye-lid opening, and marked pseudo-bulbar palsy]. 1578 4