. Melatonin Receptor Agonists

Question 1

What is the function of Melatonin receptors?

Answer 1

maintain circadian rhythms underling the sleep-wake cycle.

Located in the suprachiasmatic nuclei (SCN) of the brain.

Question 2

What are the melatonin receptor agonist?

Answer 2

Ramelteon (Rozerem®) Only one commercially available MT receptor agonist

Tasimelteon- approve TX of Non 24 hr sleep disorder

Question 3

What is the MOA of Melatonin receptor agonist?

Answer 3

Selectively binds to
MT1 & MT2 receptors in
the SCN.

MT1 = regulates sleepiness
MT2 = regulates phase-shifting effect of melatonin
(day-shift to night-shift)

Question 4

What is the approved TX of Ramelteon?

Answer 4

sleep-onset insomnia (e.g., jet-lag).

Question 5

What is the Pharmakinetics of Ramelteon?

Answer 5

Undergoes extensive first-pass metabolism by
CYP1A2. CAUTION: CYP1A2 inhibitors (ciprofloxacin)
- Plasma t1/2 is 1-3 hr.

Question 6

What is the therapeutic effects of Ramelteon?

Answer 6

• ↓ Sleep latency by 8-15 min

- ↑ Sleep time by 12-19 min

Question 7

What are the adverse effects of Ramelteon?

Answer 7

• CNS: somnolence, dizziness, fatigue, hallucinations and bizarre behavior.
  
  • Reproductive: ↑ serum prolactin — infertility & ↓ libido
  • Other: angioedema, anaphylaxis - - dyspnea, nausea

Question 8

What is the approved treatment for Tasimelteon?

Answer 8

Non-24 hr SLEEP DISORDER (i.e., NON-24)

Question 9

What is the MOA of Tasimelteon?

Answer 9

Agonist at MT2 > MT1 receptors

Question 10

What is the Pharmacokinetics of Tasimeteon?

Answer 10

• Plasma t1/2 is 0.5-3 hr
  
  • Undergoes extensive first-pass metabolism by
    CYP1A2 & CYP3A4. CAUTION: CYP1A2 (fluvoxamine) & CYP3A4 (ketoconozole) inhibitors & CYP3A4
    INDUCERS (rifampin)

Question 11

What is the therapeutic effect of Tasimelteon?

Answer 11

↑ Sleep onset and sleep maintenance

Question 12

What is the adverse effects of Tasimelteon?

Answer 12

• CNS: nightmares, abnormal dreams, UTI