Posted by Hugh on September 23, 2019, at 10:21:44
A hypothesis for the mechanism of depression implicates deficits in GABA and downstream alterations in monoaminergic neurotransmission, supported by evidence that reduced GABA levels have been observed in plasma, cerebrospinal fluid, and cortical brain tissues of patients with depression.
Neurosteroids, which are synthesized from cholesterol in the brain, are potent modulators of GABA and glutamate, because despite their steroid structure, their target activity and pharmacologic characteristics are distinct from those of glucocorticoids and differ in both genomic and nongenomic effects.
In preclinical studies, investigators have found that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA receptors, which affects both phasic and tonic inhibition of neurons.
SAGE-217, developed by Sage Therapeutics, was given an expedited development plan in 2018 following a Breakthrough Therapy meeting with FDA officials that includes an additional placebo-controlled phase 3 trial in patients with MDD, as well as the designation of an ongoing placebo phase 3 trial in patients with postpartum depression as a pivotal study.
Complete article:
poster:Hugh
thread:1106222
URL: http://www.dr-bob.org/babble/20190728/msgs/1106222.html