SSRI

links: Drugs reference: 4-30-2021

SSRIs #

• Selective Serotonin reuptake inhibitors.

• Not supposed to bind to serotonin receptors, but SERT.

• Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes

  • Fluoxetine, Sertraline, and paroxetine decrease the Km of the conversion of 5α-DHP to Allopregnanolone by human 3α-HSD type III 10- to 30-fold. Only Sertraline inhibited the reverse oxidative reaction
  • Fluox slightly inhibits 20α-HSD.
  • Paroxetine alters 17β-HSD

• [SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake]

• Some research suggests they depend on the release of histamine, by activating the 5-HT2C receptor. If one has already high histamine, things could get even worse.

• Serotonin transmission is elevated in depression. Acute SSRI treatment exacerbates ruminative processes and worsens symptoms. Chronic SSRI treatment reverses ruminative processes and reduces symptoms. R

• Antidepressant responses to SSRIs are abolished in mice unable to synthesize histamine. R

• Citalopram increased histamine levels, and a 5-HT1/5-HT2 antagonist abolished this effect.