Generic Name

Pramipexole

Mechanism

• Selective agonist for brain dopamine D₂ and D₃ receptors, with ~5‑10× higher affinity for D₃.
• Activates postsynaptic dopaminergic pathways → ↑ acetylcholine release inhibition → symptom relief.
• Short‑action, non‑competitive (partial) stimulation, producing minimal receptor desensitization compared with full agonists.

Pharmacokinetics

• Absorption: Oral, 70–80 % bioavailability; peak plasma concentration (Tmax) 6–8 h.
• Distribution: Widely distributed; crosses blood‑brain barrier; protein binding ~80 %.
• Metabolism: Pulmonary, hepatic oxidation → inactive carboxylic acid; not CYP‑450 dependent.
• Elimination: Renal excretion (~90 % unchanged); half‑life 8–12 h (short‑acting), 10–20 h (extended‑release).
• Drug interactions: Minimal; avoid concomitant MAO‑B inhibitors (risk of excessive dopaminergic effect).

Indications

• Parkinson’s disease – early to advanced stages, as monotherapy or adjunct to levodopa/carbidopa.
• Restless‑leg syndrome (RLS) – idiopathic or secondary to iron deficiency, uremia, or pregnancy.

Contraindications

• Hypersensitivity to pramipexole or any excipient.
• Uncontrolled seizures or epileptiform activity.
• Severe hepatic impairment (data limited).
• Warning: May precipitate or exacerbate impulse‑control disorders (ICDs) – gambling, hypersexuality, compulsive shopping.
• Monitor for orthostatic hypotension, especially in hypertensive elderly patients.

Dosing

• Initiate on a “go‑low–go‑slow” schedule to mitigate nausea and orthostatic hypotension.
• For extended‑release, take at bedtime; for short‑acting, can take at night or morning depending on symptom burden.

Adverse Effects

• Common: Nausea, constipation, somnolence, dizziness, orthostatic hypotension, edema.
• Serious / rare:
• Impulse‑control disorders (punding, compulsive buying, gambling).
• Severe orthostatic hypotension leading to falls.
• Priapism (rare).
• Pulmonary hypertension (very rare).
• Severe edema or fluid retention.

Monitoring

• Baseline: Neurological exam, weight, blood pressure, renal function, psychiatric history.
• Ongoing:
• Monthly weight checks (≥ 5 % gain flags fluid retention).
• Blood pressure at each visit (orthostatic systolic < 90 mm Hg).
• Neurological and motor function scales (UPDRS).
• Screening for ICDs: inquire about gambling, sexual behavior, compulsive shopping.
• Lab: Routine blood counts once, renal panel every 3–6 months.

Clinical Pearls

• Start low, go slow: A 0.125 mg nightly dose mitigates nausea; titrate only after 2–3 weeks.
• Choose formulation by convenience: Short‑acting dosing suits patients needing morning motor relief; ER preferred for bedtime-only symptoms.
• Beware of ICDs: In patients with a history of gambling, binge eating, or substance misuse, consider a dopamine agonist other than pramipexole or implement a strict monitoring protocol.
• Discontinuation warnings: Abrupt cessation can precipitate a ‘dopamine withdrawal syndrome’ (nausea, insomnia, anxiety). Taper over 4–6 weeks.
• RLS dosing nuance: Start at 0.125 mg at bedtime; most patients reach 1.25 mg within 6–8 weeks, balancing efficacy with minimal daytime somnolence.
• Pregnancy & lactation: Data limited; generally avoid during pregnancy; minimal excretion in breast milk but not enough to recommend discontinuation if breastfeeding is desired.

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• Pramipexole is a versatile dopamine agonist that, when titrated carefully and monitored diligently, offers substantial benefit for Parkinson’s disease and restless‑leg syndrome while minimizing risk of nausea, orthostatic hypotension, and impulse‑control complications.