Neurosci Lett. 2005 Mar 29;377(2):106-9.
Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.
Pan T, Xie W, Jankovic J, Le W.
Department of Neurology, Parkinson Disease Research Laboratory, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Pramipexole (PRX) is a non-ergot dopamine (DA) D(2)/D(3) receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10muM significantly increased DAT mRNA levels by 54-130% in 4-8h, VMAT2 mRNA levels by 34% in 4h, and Nurr1 mRNA levels by 31-39% in 2-4h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2h treatment of PRX. Nafadotride, a D(3) DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D(2) DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D(3) DA receptor.

Addiction. 2005 Mar;100 Suppl 1:12-22.
Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.
Ciraulo DA, Sarid-Segal O, Knapp CM, Ciraulo AM, Locastro J, Bloch DA, Montgomery MA, Leiderman DB, Elkashef A.
Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA.

ABSTRACT Aims The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. Design A multi-arm, modified blinded, placebo-controlled design was used. Setting The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). Participants Participants met criteria for cocaine dependence during a 2-week screening period. Intervention Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. Measurements Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. Findings None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. Conclusions This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

Curr Neurol Neurosci Rep. 2003 Jul;3(4):289-95.
Parkinson's disease: is the initial treatment established?
Ahlskog JE.
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Recent studies have suggested that initial dopamine agonist therapy with pramipexole or ropinirole may slow the progression of Parkinson's disease (PD) and also reduce the subsequent risk of levodopa motor complications. This presumed effect on PD progression, however, could be artifactual, resulting from the influence of chronic drug treatment on regulation of dopamine system proteins. With respect to levodopa motor complications, there is no dispute that pramipexole and ropinirole are effective in reducing levodopa dyskinesias and motor fluctuations; however, it is not clear that they must be started early, as opposed to initiation only after the levodopa complications develop. Levodopa therapy has numerous advantages that include greater efficacy, much lesser expense, simpler administration, and a lower frequency of hallucinosis and somnolence. Carbidopa/levodopa, pramipexole, and ropinirole are all appropriate first choices in the treatment of PD.

1353-8020 2001 Apr;7(2):115-120
The long-term safety and efficacy of pramipexole in advanced Parkinson's disease
Weiner WJ, Factor SA, Jankovic J, Hauser RA, Tetrud JW, Waters CH, Shulman LM, Glassman PM, Beck B, Paume D, Doyle C
Department of Neurology, University of Miami School of Medicine, 1501 N.W. 9 Avenue, 33136, Miami, FL, USA

Objective: To assess the long-term safety and efficacy of pramipexole in advanced Parkinson's disease over a four year time period.Methods: This study is an open-label extension trial of pramipexole for Parkinson's disease open to patients completing a double-blind placebo controlled safety and efficacy trial of this drug. Three hundred and six patients entered the trial. These patients had moderate to severe PD (stage II-IV Hoehn and Yahr during off time) and were experiencing motor fluctuations. Patients were titrated over a six week period and then entered a maintenance phase which lasted up to 50 months. Patients were evaluated every 3 months using the Unified Parkinson's Disease Rating Scale (UPDRS II, III and IV) and modified Schwab and England scale (S/E).Results: Sixty-four percent (197) of the 306 patients who entered this study completed it. Patients showed steady improvement over the 6 week ascending dose interval when pramipexole was reintroduced into the trial as the open-label study medication. Over the duration of the trial patients slowly returned to their baseline levels. This was true for all measures evaluated except for the UPDRS part IV. On UPDRS part IV patients remained below their baseline score which indicated an improvement for the duration of the study. Patterns similar to the overall scores were seen when the individual components of the UPDRS scale part II for "on" and "off" periods and part III were evaluated. However tremor during "on" periods showed improvement over baseline for the duration of the trial. The most common adverse events secondary to pramipexole occurring in greater than 10% of patients included dyskinesias, asymptomatic orthostatic hypotension, dizziness, insomnia, and hallucinations.Conclusion: Pramipexole was well tolerated for up to 4 years. Pramipexole treatment appeared to show continued efficacy in the treatment of Parkinson's disease for 3 years in this open-label descriptive study. After 3 years there was a gradual return to baseline motor states perhaps suggesting progression of Parkinson's disease.

Drug information

Substance: pramipexole dihydrochloride
Product Brand Name: Mirapex ®

1. Why is this drug prescribed? Although it is not a cure, Mirapex eases the symptoms of Parkinson's disease--a progressive disorder marked by muscle rigidity, weakness, shaking, tremor, and eventually difficulty with walking and talking. Parkinson's disease results from a shortage of the chemical messenger dopamine in certain areas of the brain. Mirapex is believed to work by boosting the action of whatever dopamine is available. The drug can be used with other Parkinson's medications such as Eldepryl, Sinemet, and Larodopa.

2. Most important fact about this drug: If you are taking Sinemet or Larodopa, Mirapex may allow a reduction in your dosage. And if you suffer from the "on-off" effect that often develops during Parkinson's therapy (symptom-free periods alternating with severe attacks), Mirapex may extend the good "on" times and shorten your "off" periods.

3. How should you take this medication? Take Mirapex exactly as prescribed. If it makes you nauseous, try taking it with food.
When discontinuing Mirapex therapy, it's best to do it gradually. Your doctor will tell you how to taper your dose over a week's time.
• If you miss a dose...
Take it as soon as you remember. If it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Do not take 2 doses at the same time.
• Storage instructions...
Store at room temperature; protect from light.

4. What side effects may occur? Side effects cannot be anticipated. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Mirapex.
• More common side effects may include:
Abnormal dreams, arthritis, chest pain, confusion, constipation, decreased sensitivity to touch, difficulty breathing, difficulty walking, dizziness, dizziness upon standing, drowsiness, dry mouth, hallucinations, increased muscle tone, increased urination, insomnia, involuntary movement (jerky motions), lack of appetite, memory loss, nasal inflammation, nausea, swelling, urinary tract infections, vision abnormalities, weakness
• Less common side effects may include:
Decreased sex drive, delusions, difficulty swallowing, fever, general feeling of illness, impotence, inability to hold urine, muscle spasms or twitching, pneumonia, skin disorders, thinking abnormalities, uncontrollable restlessness, unfounded suspicions, weight loss
• Rare side effects may include:
Abnormal ejaculation, abnormal heartbeat, agitation, blood clots, blood in urine, blood circulation problems, convulsions, difficult or painful urination, enlarged abdomen, eye disorders, heart attack, heart problems, joint problems, lung problems, mental illness, muscular problems, prostate problems, severe chest pain (angina), thirst

5. Why should this drug not be prescribed? If Mirapex gives you an allergic reaction, you'll be unable to use it.

6. Special warnings about this medication: Mirapex can cause your blood pressure to drop when you first stand up, resulting in symptoms such as dizziness, nausea, fainting, blackouts, and, sometimes, sweating. To avoid or reduce these symptoms, try to stand up slowly, especially at the beginning of treatment with Mirapex.
Mirapex can cause drowsiness and may trigger hallucinations, especially if you are over 65 or have an advanced case of Parkinson's. You may even fall asleep--without warning and without feeling drowsy--while performing everyday activities. Check with your doctor immediately if you find that you're getting drowsy or falling asleep while eating, talking, or watching television. Do not drive a car or undertake other dangerous activities until you've spoken with the doctor. Be especially cautious when taking other drugs that cause sleepiness.
If you have a kidney condition, make sure the doctor is aware of it. You'll probably need regular blood tests to check your kidney function, and your dosage of Mirapex may have to be reduced.
In very rare cases, Mirapex may cause muscle wasting. If you develop muscle aches or soreness after you start Mirapex, be sure to tell your doctor. Also alert your doctor if you notice any changes in your eyesight.

7. Possible food and drug interactions when taking this medication: If Mirapex is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Mirapex with the following:

Carbidopa/Levodopa (Sinemet)
Sedatives and tranquilizers such as chloral hydrate, codeine products, Dalmane, Halcion, and phenobarbital
Cimetidine (Tagamet)
Diltiazem (Cardizem, Dilacor XR)
Major tranquilizers such as Compazine, Haldol, Mellaril, Navane, Prolixin, Stelazine, and Thorazine
Metoclopramide (Reglan)
Quinidine (Quinidex, Quinaglute)
Quinine
Ranitidine (Zantac)
Triamterene (Dyrenium)
Verapamil (Calan, Isoptin)

Combining Mirapex with Sinemet or Larodopa sometimes triggers twitching and jerky movements. If this happens, tell your doctor. A reduction in your dose of Sinemet or Larodopa may solve the problem.

8. Special information if you are pregnant or breastfeeding: The effects of Mirapex during pregnancy have not been adequately studied, so it's best to avoid it if you're expecting. If you are pregnant or plan to become pregnant, inform your doctor immediately.
It is not known whether Mirapex appears in breast milk. If the drug is considered essential to your health, your doctor may advise you to stop breastfeeding while taking the medication.

9. Recommended dosage:

ADULTS

The usual starting dose is 0.125 milligrams 3 times a day. If necessary, your doctor may increase the dose every 5 to 7 days until the maximum dose of 4.5 milligrams a day is reached. Dosage is usually increased gradually to minimize the drug's potential side effects. If you have kidney disease, the doctor will keep the dosage quite low.

CHILDREN

The safety and effectiveness of this drug in children have not been established.

10. Overdosage: Although there is no information on Mirapex overdose, any medication taken in excess can have dangerous consequences. If you suspect an overdose, seek medical attention immediately.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov

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MIRAPEX (MIRAPEXIN)
Generic name: Pramipexole dihydrochloride

Health information and new

Dosage	Packing	Price	Pay now
0,18 mg (0.25 mg pramipexole dihydrochloride)	30 tab	USD 45.00
0,7 mg (1 mg pramipexole dihydrochloride)	30 tab	USD 98.00