r/anhedonia

Fluoxetine

• 
• SSRI
• Fluoxetine can affect the electrical currents that heart muscle cells use to coordinate their contraction, specifically the potassium currents Ito and IKs that repolarise the cardiac action potential. Under certain circumstances, this can lead to prolongation of the QT interval, a measurement made on an electrocardiogram reflecting how long it takes for the heart to electrically recharge after each heartbeat. When fluoxetine is taken alongside other drugs that prolong the QT interval, or by those with a susceptibility to long QT syndrome, there is a small risk of potentially lethal abnormal heart rhythms such as torsades de pointes. A study completed in 2011 found that fluoxetine does not alter the QT interval and has no clinically meaningful effects on the cardiac action potential.
• Fluoxetine is a potent inhibitor of CYP2D6 enzymes.
• Patients who are taking NSAIDs, antiplatelet drugs, anticoagulants, omega-3 fatty acids, vitamin E, and garlic supplements must be careful when taking fluoxetine or other SSRIs, as they can sometimes increase the blood-thinning effects of these medications.
• Fluoxetine inhibit many isozymes of the cytochrome P450 system that are involved in drug metabolism.
• Potent inhibitor of CYP2D6 (which is also the chief enzyme responsible for their metabolism) and CYP2C19, and mild to moderate inhibitors of CYP2B6 and CYP2C9.
• They also inhibit the activity of P-glycoprotein, a type of membrane transport protein that plays an important role in drug transport and metabolism and hence P-glycoprotein substrates, such as loperamide, may have their central effects potentiated.
• Binding affinities (Ki in nM)

• Molecular Target	Fluoxetine
  SERT	1
  NET	660
  DAT	4180
  5-HT1A	32400
  5-HT2A	147
  5-HT2C	112
  α1	3800
  M1	702-1030
  M2	2700
  M3	1000
  M4	2900
  M5	2700
  H1	3'250

• Increases the concentration of circulating allopregnanolone, a potent GABAA receptor positive allosteric modulator, at concentrations that are inactive on serotonin reuptake.
• Has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine.
• Channel blocker of anoctamin 1, a calcium-activated chloride channel.
• A number of other ion channels, including nicotinic acetylcholine receptors and 5-HT3 receptors, are also known to be inhibited at similar concentrations.
• Fluoxetine has been shown to inhibit acid sphingomyelinase, a key regulator of ceramide levels which derives ceramide from sphingomyelin.
• The bioavailability of fluoxetine is relatively high (72%).
• Peak plasma concentrations are reached in 6–8 hours.