Psychopharmacology
Antidepressants' Mechanism of Action
Monoamine Oxidase Inhibitors (MAOIs)
Examples
- Tranylcypromine, isocarboxazid, phenelzine, and selegeline (a selective MAO-B inhibitor).
Mechanism
- MAO Inhibitors block MAO metabolization of neurotransmitters (we show NE and 5-HT in our diagram), which keeps more of the neurotransmitters actively available.
- Older MAOIs inhibit both MAO-A, which metabolizes norepinephrine (NE), serotonin (5-HT), and tyramine, and also MAO-B, which metabolizes dopamine (DA), but newer, selective MAO-B inhibitors (eg, selegeline) also exist.
Tricyclic antidepressants (TCAs)
Examples
- The -triptyline's (amitriptyline, nortriptyline, and protriptyline); the -ipramine's (clomipramine, desipramine, imipramine, and trimipramine maleate); and doxepin.
Mechanism
- TCAs block NE reuptake and 5-HT reuptake and also block histamine (H1) receptors, muscarinic (acetylcholine) receptors, and alpha-adrenergic receptors, and thus they have fairly robust side effects.
Structure
- As their name suggests, tricyclic antidepressants consist of a three-ringed structure with an attached amine, which is either secondary or tertiary.
- Secondary amines (including desipramine, nortriptyline, and protriptyline) have a greater norepinephrine reuptake inhibition, whereas, tertiary amines (including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine) have greater serotonin reuptake inhibition.
- As a chemistry reminder, secondary amines have a nitrogen bound to two carbons whereas tertiary amines have a nitrogen bound to three carbons.
Selective serotonin reuptake inhibitors (SSRIs)
Examples
- The -oxetine's (fluoxetine and paroxetine); the -alopram's (citalopram and escitalopram); sertraline; and fluvoxamine.
Mechanism
- SSRIs block serotonin reuptake into the presynaptic axon terminal; specifically, they block the serotonin transporter (SERT).
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Examples
- The -lafaxine's (desvenlafaxine, venlafaxine); the -naciprin's (levomilnaciprin, milnacipran); and duloxetine.
Mechanisms
- SNRIs inhibit both NE reuptake and also 5-HT reuptake.
Atypical antidepressants
Buproprion
- Norepinephrine and dopamine reuptake inhibitor.
- Presynaptic alpha-2 blocker.
- This receptor inhibits NE release, thus blockade of it results in NE release.
- Also a 5-HT subreceptor antagonist; the effects of this are less intuitive but can increase serotonin levels to impact non-inhibited subreceptors.
- And an H1 blocker, as well.
- Inhibits SERT and 5-HT receptors, which has complicated effects but overall increases serotonin levels and is a potential contributor to serotonin syndrome.
- Nicotinic partial acetylcholine receptor agonist.
- We can remember its mechanism by associating "nicline" is used for nicotine cravings to help in smoking cessation.
- Serotinergic agents that block 5-HT reuptake.