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PubMed1999

The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson's disease.

Single-photon emission computed tomography (SPECT) imaging with the dopamine transporter ligand, [123I] beta-CIT (2beta-carboxymethoxy-3beta-[4-iodophenyl] tropane), has been proposed as a means of measuring Parkinson's disease (PD) progression. To be useful in this role, however, [123I] beta-CIT imaging should not be influenced by the medications used to treat PD, including the dopamine agonist drugs such as pergolide. We assessed the effect of adjunctive pergolide administration on [123I] beta-CIT uptake in 12 patients with PD, who were being treated with levodopa, initiating pergolide therapy for motor fluctuations. Patients underwent [123I] beta-CIT imaging at baseline, subsequently while on pergolide therapy (6 weeks), and again 4 weeks after pergolide wash-out. Uptake in the striatum was averaged for the two sides and expressed as (striatum - occipital)/occipital, with similar calculations for putamen and caudate. Consistent with PD, the patients' mean striatal and putamen uptake ratios at baseline were significantly less (p <0.001) than the mean values from 26 normal control subjects of similar age. During pergolide treatment, the striatal and putamen [123I] beta-CIT uptake ratios were each statistically similar to baseline, although there was a slight trend toward an increased striatal value (8% higher on pergolide; p = 0.105). Caudate [123I] beta-CIT uptake was 11% higher on pergolide therapy (nominal p = 0.042, but not significant when adjusted for multiple comparisons: p = 0.126). After pergolide wash-out, the striatal, putamen, and caudate uptake ratios did not differ from baseline. Therefore, we found that pergolide therapy did not significantly affect [123I] beta-CIT SPECT imaging but we cannot exclude a small influence.

Aged↗
PubMed1989

Chronic activation of dopamine receptors in the female infantile rat: effect on hypophyseal hormones and on the onset of puberty.

In the female rat the period from days 7-20 of age is special with regard to regulation of hypophyseal hormone secretion. This period is characterized by high FSH levels and the occurrence of sporadic LH peaks. As it has been reported that haloperidol could enhance both gonadotropins at 12 days of age and not at later ages, it was of interest to treat rats during the infantile period with pergolide, a dopaminergic agent of long action, and evaluate its effect on hormone levels and puberty onset. Three different schedules of drug injections were applied: 1) daily injections (0.05 mg/kg.day) on days 1-10, 2) daily injections on days 5-14, and 3) daily injections on days 11-20. It was found that only animals treated with daily injections of pergolide on days 11-20 showed an advance in the age of vaginal opening and first estrus compared to distilled water-injected controls. Thus, the rest of the experiments were performed using injection schedule 3. In this group of animals serum LH and FSH levels were decreased 3 and 6 days after the beginning of pergolide treatment (13 and 16 days of age); at 19 days of age pergolide did not modify gonadotropin levels. One day after the end of pergolide treatment (day 21 of age), there was a rebound in LH levels in drug-injected rats, and a nonsignificant increment in FSH levels was observed. There were no differences in serum gonadotropin levels on days 22, 23, and 25 or peripubertally (29, 33, or 36 days of age). On the other hand, pergolide did not significantly modify PRL levels during the treatment, probably due to the already low values of PRL at these ages. Furthermore, PRL levels were not different between control and pergolide-injected rats at all other ages studied. After puberty onset, animals were observed for eight consecutive cycles, and both groups cycled regularly. Furthermore, PRL and gonadotropins levels were similar at diestrus and proestrus. To evaluate if pergolide treatment during the infantile period had caused permanent alteration in dopamine receptor sensitivity, animals were injected with haloperidol (0.1 or 0.25 mg/kg), and PRL release was evaluated. There were no differences in the hyperprolactinemic effect of the drug between groups. Finally, gonadotropin sensitivity to LHRH was similar in adult female rats in proestrus of both groups. The present results suggest that chronic activation of dopamine receptors during the infantile period evokes specific responses on gonadotropin secretion and advances the age of puberty onset.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Restless legs syndrome and its treatment by dopamine agonists.

The restless legs syndrome (RLS) characteristically presents with an irresistible urge to move that is most often accompanied by creeping sensations deep in the limbs. Occasionally the upper limbs can also be affected. RLS symptoms occur at rest and are typically more intense at night and at bedtime. Some patients complain about involuntary leg movements, so-called periodic limb movements (PLM), while at rest or PLM have been observed by the bed partner. Often, patients have to get out of bed several times at night, to relieve themselves of their disagreeable sensations.The prevalence of RLS is estimated to be about 5%. Up to now only three classes of drugs have been systematically evaluated for treatment of RLS: benzodiazepines, opioids and dopaminergic agents.The most consistent results have been obtained with dopaminergic drugs. Several studies have shown that L-dopa given with a peripheral decarboxylase inhibitor at a 10:4 ratio is effective in treating RLS. Controlled studies using polysomnographic recordings in a double-blind design showed that L-dopa administered at night produces a significant reduction of RLS occurring at bedtime and of PLM, which are often associated with nocturnal arousals. In most cases, L-dopa 100mg, in conjunction with the decarboxylase inhibitor carbidopa or benserazide 25mg, suppresses RLS although a rebound of PLM may be observed in the last part of the night. The two major adverse effects frequently seen in patients treated with L-dopa are:Augmentation is one of the limiting factors of L-dopa therapy; thus, alternative treatment options are of major interest. In several open treatment trials performed with pergolide, patients reported a marked improvement of RLS symptoms including sleep problems. Mild symptoms of augmentation under pergolide treatment have been reported from single patients. In another 6-month open label trial, pergolide proved to be effective in patients who developed augmentation under L-dopa by relieving daytime symptoms after switching to pergolide.Most recently, the results of these open label trials have been replicated in a randomized, placebo-controlled, double-blind multicenter trial. Treatment with a single evening dose of 0.25-0.75mg pergolide resulted in a significant improvement of almost all subjective and objective parameters. Under pergolide, patients rated their RLS symptoms and sleep disturbances much less severe and polysomnographic recordings also revealed a significant improvement of all important sleep parameters. To prevent peripheral side-effects such as nausea or orthostatic hypotension, pergolide should be slowly up-titrated or domperidone should be added. Under these conditions, no major side-effects have been observed in treatment trials with pergolide in dosages up to 1.25mg.Pergolide with a half-life of 12-16h thus appears to be an appropriate drug in the therapy of RLS especially in those patients who developed augmentation under L-dopa therapy. Owing to the remarkable therapeutic effect of pergolide on RLS symptom control, other dopamine agonists are presently being tested for the treatment of RLS.

Journal Article↗
PubMed1996

Dopamine receptor affinities in vitro and stereotypic activities in vivo of cabergoline in rats.

An ergot alkaloid derivative, cabergoline, and its metabolites were investigated for their affinities for dopamine D1 and D2 receptors in rat striatum in vitro in comparison with those of bromocriptine and pergolide. The affinity for D1 receptors was in the following order: pergolide > des-dimethylaminopropyl cabergoline (FCE21904) > cabergoline > or = bromocriptine > or = des-methyl cabergoline (FCE27395) > or = des-ethylcarbamoyl cabergoline (FCE21590). From the effects of GTP on these affinities for the D1 receptor, cabergoline, some of its metabolites, and pergolide were characterized as agonists in contrast to bromocriptine which was classified as an antagonist. The affinity for D2 receptors was ranked as follows: pergolide > or = cabergoline > or = FCE27395 > or = FCE21904 > bromocriptine > FCE21590 > carboxylic acid-type derivative of cabergoline (FCE21589). The affinity of each compound for the D2 receptor was much higher than that for the D1 receptor. The selectivity of cabergoline for D2 receptor was higher than those of bromocriptine and pergolide. Furthermore, these ergot alkaloids were investigated for eliciting stereotypy after subcutaneous administration to normal rats. Pergolide potently induced stereotypy at doses of 0.5 and 1.0 mg/kg, cabergoline slightly induced it only at a high dose of 2.0 mg/kg, whereas bromocriptine did not induce it at any of the doses tested, 10-40 mg/kg. These results suggest that pharmacological properties of cabergoline for the D1 and D2 receptors differ from those of bromocriptine and pergolide.

Animals↗