What is apomorphine?

Apomorphine: Clinical Applications and Pharmacological Properties

Apomorphine is a potent, direct-acting dopamine agonist primarily used in advanced Parkinson's disease for rapid relief of "OFF" periods, administered subcutaneously as either intermittent injections or continuous infusions.

Pharmacological Properties

• Mechanism of Action:

  • Non-selective dopamine agonist that activates all dopamine receptor subtypes (D₁, D₂S, D₂L, D₃, D₄, and D₅) 1
  • Also has affinity for serotonin receptors (5HT₁A, 5HT₂A, 5HT₂B, and 5HT₂C) and α-adrenergic receptors 2
  • Increases vagal tone, which can affect cardiac autonomic function 3

• Pharmacokinetics:

  • Highly lipophilic compound that rapidly crosses the blood-brain barrier 4
  • Short-acting with rapid onset of action (7-10 minutes) 1
  • Short elimination half-life (30-90 minutes) 4
  • High clearance drug (3-5 L/kg/h), primarily metabolized by the liver 4
  • Only 3-4% excreted unchanged in urine 4

Clinical Applications

1. Parkinson's Disease Management

• Primary indication: Advanced Parkinson's disease with motor fluctuations not adequately controlled by levodopa or other dopamine agonists 5
• Administration methods:
  • Intermittent subcutaneous injections for rapid relief of unpredictable "OFF" periods
  • Continuous subcutaneous infusion for reducing daily "OFF" time (approximately 50% reduction) 5
• Dosing:
  • Available as 98 mg/20 mL (4.9 mg/mL) solution in single-dose prefilled cartridges 6
  • Maximum continuous dosage: 6 mg/hour over waking day (typically 16 hours) 6
  • Extra doses (0.5-2 mg) may be used for breakthrough symptoms, maximum 3 per day 6
  • Maximum total daily dosage: 98 mg 6

2. Other Applications

• Veterinary medicine: Used to induce vomiting in dogs for treatment of certain poisonings 2
• Historical uses: Treatment of addiction (heroin, alcohol, cigarettes), erectile dysfunction, and hypoactive sexual desire disorder 2
• Emerging research: Potential role in Alzheimer's disease treatment by stimulating Aβ catabolism 2

Contraindications

• Absolute contraindications:
  • Concomitant use of 5HT₃ antagonists (e.g., ondansetron, granisetron) due to risk of profound hypotension and loss of consciousness 6
  • Hypersensitivity/allergic reaction to apomorphine or excipients, including sulfites 6
  • Intravenous administration (risk of thrombus formation and pulmonary embolism) 6

Adverse Effects

• Common adverse effects:

  • Nausea and vomiting (22% and 7% of patients, respectively) 6
  • Somnolence (22% of patients) 6
  • Skin reactions at injection site 5
  • Hypotension 3

• Serious concerns:

  • Risk of falling asleep during activities of daily living 6
  • Potential for cardiac effects due to vagal tone changes 3

Special Populations

• Renal impairment:
  • For mild to moderate renal impairment: Initial extra dose should be 0.5-1 mg and not exceed 1 mg 6
  • Patients with severe renal impairment have not been studied 6

Clinical Pearls

• Apomorphine has efficacy equal to levodopa but with shorter onset and duration of action 5
• Despite its name, apomorphine has no opioid activity and is pharmacologically distinct from morphine 4
• Antiemetic pretreatment is often necessary to manage nausea and vomiting 6
• Avoid abrupt discontinuation to prevent worsening of Parkinson's disease symptoms 6
• Patients should be monitored for excessive drowsiness and warned about the risk of falling asleep during activities 6

Apomorphine represents an important option for managing advanced Parkinson's disease when conventional therapies fail to control motor fluctuations, with its rapid onset making it particularly valuable for addressing sudden "OFF" periods.