Brexanolone: Difference between revisions
From Pharmacopedia
More actions
| [unchecked revision] | [unchecked revision] |
Create Brexanolone page (Stahl-sourced detail with skepticism) |
Terminology sweep: drug/medication → medicine |
||
| Line 12: | Line 12: | ||
| halflife = ~9 hours (terminal) | | halflife = ~9 hours (terminal) | ||
| bioavailability = 100% (IV) | | bioavailability = 100% (IV) | ||
| pregnancy = | | pregnancy = Medicine is structurally identical to endogenous allopregnanolone; pregnancy considerations relate to breastfeeding during/after infusion. Limited data; brief interruption of breastfeeding considered | ||
| legal = Rx; REMS program required (excessive sedation/loss of consciousness during infusion) | | legal = Rx; REMS program required (excessive sedation/loss of consciousness during infusion) | ||
| intro = '''Brexanolone''' (brand name Zulresso) is a cyclodextrin-based IV formulation of '''allopregnanolone''', the body's own neuroactive steroid produced as a metabolite of progesterone. FDA-approved in March 2019 as the first | | intro = '''Brexanolone''' (brand name Zulresso) is a cyclodextrin-based IV formulation of '''allopregnanolone''', the body's own neuroactive steroid produced as a metabolite of progesterone. FDA-approved in March 2019 as the first medicine specifically for postpartum depression (PPD). Administered as a single 60-hour continuous infusion in a REMS-certified inpatient setting due to risk of excessive sedation. The medicine's rationale rests on the observation that allopregnanolone levels fall precipitously after delivery; rapidly restoring those levels via infusion produces a rapid antidepressant response that persists for 30+ days in trials. | ||
| pharmacodynamics= Positive allosteric modulator at GABA-A receptors at a distinct '''neuroactive steroid binding site''' (separate from benzodiazepine and barbiturate sites). Modulates both '''synaptic''' (phasic, mostly benzo-sensitive α1/α2/α3/α5-containing) and '''extrasynaptic''' (tonic, mostly benzo-insensitive δ-containing) GABA-A receptors. The benzodiazepine-insensitive δ-containing extrasynaptic receptors are hypothesized to be the key target for antidepressant effect, since benzodiazepines themselves do not have antidepressant efficacy. | | pharmacodynamics= Positive allosteric modulator at GABA-A receptors at a distinct '''neuroactive steroid binding site''' (separate from benzodiazepine and barbiturate sites). Modulates both '''synaptic''' (phasic, mostly benzo-sensitive α1/α2/α3/α5-containing) and '''extrasynaptic''' (tonic, mostly benzo-insensitive δ-containing) GABA-A receptors. The benzodiazepine-insensitive δ-containing extrasynaptic receptors are hypothesized to be the key target for antidepressant effect, since benzodiazepines themselves do not have antidepressant efficacy. | ||
| effects = Sedation (very common), loss of consciousness (REMS warning), syncope, dry mouth, flushing. Suicidal thoughts have been observed. | | effects = Sedation (very common), loss of consciousness (REMS warning), syncope, dry mouth, flushing. Suicidal thoughts have been observed. | ||