Brexanolone IV (Zulresso), The first-ever drug take FDA-approval for postpartum depression in Mar 2019. continues IV infusion over 60 hrs (2.5 days).

1. Brexanolone
“The 1st FDA approved drug for Postpartum Depression”
Prof. Sawsan Aboul-Fotouh
Department of pharmacology, faculty of Medicine, Ain shams University
Brexanolone

2. Brexanolone IV (Zulresso), The first-ever drug take FDA-approval for
postpartum depression in Mar 2019. continues IV infusion over 60 hrs (2.5 days).
Brexanolone
Brexanolone
Allopregnanolone (ALLO)
(Antidepressant effect within hours (6-7hrs) and No relapse through 30 days)

3. What is Brexanolone ?
Synthetic Allopregnanolone, Neuroactive steroid NS. (GABAA ++)
produced in Suprarenal glands, Feto-placental unit, Gonads & Brain. (80 ys,
1938).
↓ NS synthesis is found in premenstrual dysphoric disorder, depression
, panic disorder , schizophrenia and bipolar disorder
(ALLO)

4. - GABA-A receptor (δ) Alterations occur 2ry
to progesterone (&ALLO) fluctuations in
menstrual cycle, pregnancy & postpartum
-ALLO affect HP axis and neurogenesis.
- ALLO ↓ in serum & CSF in depression.
- SSRI →↑ ALLO synthesis
- ALLO ↑ during Preg. (Peak in 3rd trimester)
then sudden ↓ after Labor.
(ALLO)
ALLO, is GABA A +ve
Allosteric Modulator
Depression
Brexanolone synthetic ALLO experimental
& clinical studies for Postpartum Depression
& ALLO

5. Brexanolone
Mar 2019

6. What is the Mechanism of Action of
Brexanolone in Depression ??
GABA A Positive
Allosteric Modulator ??!!
Brexanolone

7. Mechanism of action of Brexanolone:
↑ synaptogenesis
Brexanolone, a +ve allosteric modulator restores GABAergic inhibition→Rapid recovery of glutamate receptors (AMPA &NMDA) surface
expression→ Normalize Neuronal Balance (GABA/Glutamate)→ ↑BDNF & Neuroplasticity & synaptogenesis
GABAergic hypothesis of resilience

8. The most common adverse reactions (≥5%)
1. Sedation/somnolence,
2. Loss of consciousness (Monitor)
3. dry mouth, flushing/hot flush.
Pharmacokinetics
- Brexanolone half-life is ̴ 9 hours.
- It is metabolized by non-cytochrome P450
- No significant differences in the pharmacokinetics of renal or hepatic impairment.

9. 1959
Imipramine
(TCA)
1961
Amitriptyline (TCA)
Phenelzine,
tranylcypromine
(MAOI)
1981
Trazodone
(SARI)
Bupropion
(NDRI)
1985
1987
Fluoxetine
(SSRI)
1988 Maprotiline (NRISA)
1991
1993
2009
1992
Sertraline (SSRI)
Amoxapine (SNRISA)
Venlafaxine (SNRI)
1995
1997
1998
2002
2006
2008
Mirtazapine
(NASSA)
Reboxetine
(Selective NRIs)
Citalopram
(SSRI)
Escitalopram
(SSRI)
Selegiline TP
(MAOI)
Desvenlafaxine
(SNRI)
Quetiapine
(Atypical)
2013
2011
Vilazodone
(SPARI)
Vortioxetine
(SARI)
2004
Duloxetine
(SNRI)
Esketamine
Brexanolone
Glutamate/
& GABAAction
2019
?
By Dr. Esraa M Elnahas

10. Psilocybin has serotonergic +
glutamatergic action
(Hallucinogen or Psychedelic as DMT & LSD)
Magic Mushroom
Psilocybin has lower addiction liability and toxic effects compared with ketamine &and is not associated
with long-term perceptual, cognitive, or neurological dysfunction
Nov. 2020