Antidepressants Overview Quiz

Study Notes

Nefazodone

Nefazodone is less sedating than trazodone, with similar metabolism.
It's a CYP3A4 inhibitor and has idiosyncratic hepatotoxicity.
Its metabolism involves oxidative deamination, similar to trazodone.

Venlafaxine (Effexor)

Venlafaxine (Effexor) is a norepinephrine-serotonin reuptake inhibitor (NSRI).
It contains a phenethylamine moiety.
Its half-life (t_1/2) is approximately 11 hours.
At low doses, it acts as a selective serotonin reuptake inhibitor (SSRI).
At higher doses, it inhibits norepinephrine reuptake (NET) as well.

Desvenlafaxine (Pristiq)

Desvenlafaxine is the primary metabolite of venlafaxine.
It has two hydroxyl groups (a demethylated analog of venlafaxine).
Its half-life (t_1/2) is approximately 11 hours.

Fluoxetine (Prozac)

Fluoxetine is an SSRI derived from Benadryl (ABA).
Both enantiomers are active.
Its half-life (t_1/2) is approximately 50 hours, reaching steady-state in 4-5 weeks.

Norfluoxetine

Norfluoxetine is the demethylated substrate of fluoxetine.
It's not a P-gp substrate.
It's the primary metabolite of fluoxetine.

Fluoxetine SAR and Metabolism

Fluoxetine's structure, specifically its aromatic substitution, plays a crucial role in its activity and metabolism.
A substituted aromatic ring with specific substituent positions leads to differing degrees of 5-HT reuptake inhibition or norepinephrine reuptake inhibition.
Specific atoms and bond distances contribute to high selectivity towards 5-HT.
Metabolism primarily involves oxidative dealkylation.

Fluoxetine Substitution SAR

Substituting the 4 carbon position of the Fluoxetine structure increases 5-HT reuptake inhibition.
Substituting the 2 carbon position of the Fluoxetine structure increases norepinephrine reuptake inhibition.

Fluoxetine BBB Penetration

Fluoxetine's apparent blood-brain barrier penetration is relatively low, measured by an MPO, or metabolism potential.
However, it still crosses the blood-brain barrier.
The MPO (2.55) is less than the 4 required for efficient cross-barrier penetration, however it still crosses.

Sertraline (Zoloft)

Sertraline has a conformationally constrained structure.
Its structure features an aromatic ring with two chlorine atoms attached and a simple hexane ring.

Paroxetine (Paxil)

Paroxetine's structure includes an aromatic ring with an attached oxygen ring, and a fluorine substituent on another ring.

Citalopram (Celexa)

Citalopram is an SSRI administered as a racemic mixture.
It's the only tertiary amine antidepressant with a triple-bonded nitrogen moiety.
It displays high selectivity for serotonin reuptake (SERT) over norepinephrine reuptake (NET).
A quaternary carbon with an oxygen group is present in its structure

Duloxetine (Cymbalta)

Duloxetine is an SNRI administered as R-Duloxetine.
Its structure includes a naphthalene ring and an aryl bioisostere.

Description

Test your knowledge on various antidepressants including Nefazodone, Venlafaxine, Desvenlafaxine, and Fluoxetine. This quiz covers their mechanisms, pharmacokinetics, and unique properties. Perfect for students and professionals in pharmacology or psychiatry.