Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans.
Schilling JC, Adamus WS, Palluk R.
Human Pharmacology Centre, Boehringer Ingelheim KG, Germany.
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The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist, on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels were investigated in a randomized, double-blind, crossover study in 12 healthy volunteers. Single oral doses of 0.1, 0.2, and 0.3 mg pramipexole and placebo were studied over a period of 24 hours. Pramipexole decreased serum prolactin levels in a dose-dependent manner, with a maximum effect after 2 to 4 hours. Serum levels of human growth hormone were dose-dependently increased; however, this effect was only significant 2 hours after drug administration. Furthermore, a slight increase in serum cortisol levels and a slight decrease in serum thyrotropin levels was observed. Our findings show for the first time pharmacodynamic effects of pramipexole after single oral doses in healthy volunteers. The compound was well tolerated and showed an endocrine profile similar to other dopamine D2-agonists.
PMID: 1350237 [PubMed - indexed for MEDLINE]
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Increased frequency and range of sexual behavior in a patient with Parkinson's disease after use of pramipexole: a case report.
Munhoz RP, Fabiani G, Becker N, Teive HA.
Movement Disorders Unit, Neurology Service, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
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INTRODUCTION: Several recent reports have linked the use of dopamine agonists (DAs) to a variety of compulsive behaviors in patients with Parkinson's disease (PD). These inappropriate behaviors may include pathological gambling, compulsive shopping, and hypersexuality. AIM: To report the case of a patient with increased range of sexual behavior after use of pramipexole, a DA. METHODS: A 67-year-old man with a 7-year diagnosis of PD treated with levodopa and pramipexole presented with a dramatic change in sexual behavior after an increase in DA dose. RESULTS: The patient, who historically was a very shy and conservative person, started to present increased frequency of sexual intercourse with his wife, during which he began speaking obscenities with an extreme preference for anal intercourse, preferences never requested before. After pramipexole was withdrawn, complete remission was observed with return to his usual sexual behavior. CONCLUSIONS: Hypersexuality and paraphilias are complications not uncommonly found in patients with PD under dopaminergic treatment. Further studies are needed for the understanding of this complex complication, and particularly the most prevalent relationship between pathological hypersexuality and use of DAs.
PMID: 18466265 [PubMed - indexed for MEDLINE]
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Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome.
Driver-Dunckley ED, Noble BN, Hentz JG, Evidente VG, Caviness JN, Parish J, Krahn L, Adler CH.
Department of Neurology, Parkinson's Disease and Movement Disorders Center, Mayo Clinic, 13400 E. Shea Boulevard, Scottsdale, AZ 85259, USA.
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OBJECTIVES: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease. METHODS: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors. RESULTS: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits. CONCLUSIONS: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.
PMID: 17909302 [PubMed - indexed for MEDLINE]
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Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
Lemke MR, Brecht HM, Koester J, Reichmann H.
Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany.
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Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.
PMID: 16814808 [PubMed - indexed for MEDLINE]
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Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy.
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OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
PMID: 12479663 [PubMed - indexed for MEDLINE]