• Using your textbooks, draw up a classification of the drugs that are used as antidepressants.
  • Tricyclic antidepressants-

                             Tertiary amine:

• Impramine
• Amitriptyline
• Trimipramine
• Chlorimipramine

                               Secondary amine:

• Nortriptyline

• Desimipramine

• • Monoamine oxidase inhibitors - Phenelzine, Tranylcypromine, Selegiline, Moclobemide

• • Selective Serotonin reuptake inhibitors-Fluoxetine, Sertraline, Citalopram, Paroxetine, Escitalopram

• • Serotonin and noradrenalin reuptake inhibitors- Venlafaxine, Duloxetine, Desvenlafaxine

• • Selective noradrenalin reuptake inhibitors-Reboxetine

• • Tetracyclic and Unicyclic AD’s-Bupropion, Mirtazapine, Amoxapine, Maprotiline

• • Serotonin Receptor Modulator-Trazodone, Nefazodone, Vortioxetine
  • Circadian rhythm regulators- Agomelatine

• What do the existing drugs all have in common regarding their mechanisms of action?
  • They all promote monoamine activity by increasing NA and 5-HT levels at the central synapse (re-uptake inhibition, degradation inhibition or the blockage of the presynaptic α2 receptor)

• How long does it take for the antidepressive effects of these drugs to appear? What is the reason for this?

The onset of the drug is very slow and can take up to 6-8 weeks for effects to be seen. In people with depression G-proteins tend to cluster in the patches in brain cell membrane rich in cholesterol called lipid rafts. When stuck on this raft G-proteins lack access to molecules called CAMP which is necessary to work and transmits signals of serotonin.

• How do the TADs and the selective serotonin reuptake inhibitors (SSRI’s) differ in respect of?

• • Efficacy- TAD’s: needs to be titrated to the minimum effective dose

               SSRI’s: can be started on the full dose

• • Side effects-
  • TAD’s: sedation, tremors, insomnia, disturbed vision, dry mouth, urinary retention, confusion, orthostatic hypotension, dysrhythmias convulsions, weight gain and sexual dysfunction. 
  • SSRI’s: Insomnia, tremors, GIT disturbances, headache, ↓ libido, sexual    dysfunction, anxiety (acute), EPS, withdrawal syndrome. ↓ appetite, non-sedating, acute increase in 5-HT synaptic activity initially causes acute anxiety, later 5-HT decreases again

Safety?

-TAD’s: Not safe in overdose but it is commonly the drug used for suicide.

-SSRI’s: safer with regards to overdose.

• What is the action of mirtazapine?

Blocks:

• a2: Increases NA & Increase 5-HT release
• 5-HT2A: antidepressant effect
• 5-HT3: anxiolytic; decrease nausea
• H1 & a1
• Indirect stimulation of 5-HT_1A: anxiolytic

• What is the action of venlafaxine?

Blocks both 5-HT and NA re-uptake; more potent for 5-HT than for NA

• What is the action of agomelatine?

MT1 and MT2 receptor agonist; also 5-HT2C antagonist with antidepressant properties

Brand, L. 2021. Antidepressants. SU. 10 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education