Brain allopregnanolone regulates the potency of the GABAA receptor agonist muscimol

  title={Brain allopregnanolone regulates the potency of the GABAA receptor agonist muscimol},
  author={Graziano Pinna and Veska Uzunova and Kinzo Matsumoto and Giulia Puia and Alessandro Guidotti},

Brain 5α-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation

Protracted social isolation in mice may provide a model to investigate whether 5α-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonist, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABAA receptors.

Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective

Multifunctional aspects of allopregnanolone in stress and related disorders

  • Anjana BaliA. Jaggi
  • Biology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2014



Does neurosteroid modulatory efficacy depend on GABAA receptor subunit composition?

A direct activation of Cl- current by 3 alpha-OH-DHP was observed in native and recombinant receptors but its efficacy on the various molecular forms of GABAA receptor tested was always smaller than that of identical concentrations (10 microM) of GABA.

Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain.

The presence of allopregnanolone and allotetrahydroDOC in brain is demonstrated and acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.

Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.

Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability.

Pharmacology of Neurosteroid Biosynthesis. Role of the Mitochondrial DBI Receptor (MDR) Complex

DBI is the acronym for diazepam binding inhibitor and refers to a 9-kd endogenous polypeptide first purified from rat brain by monitoring this peptide's ability to displace [3H]-diazepam specifically

Modulation of the GABAA receptor by progesterone metabolites

The results suggest that certain naturally occurring steroids potentiate the actions of GABA and, additionally, directly activate the GABAA receptor.

A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons.

Based upon some of the unique characteristics of the epalons relative to barbiturates and the BZs, it is plausible that the epAlons can be developed into a novel class of therapeutic agents for the treatment of anxiety, epilepsy, and insomnia.

Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery.

The results indicate that the plasticity of GABAA receptors during pregnancy and after delivery is functionally related to fluctuations in endogenous brain concentrations of AP whose rate of synthesis/metabolism appears to differ in the brain, compared with plasma, in pregnant rats.

Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation.

Although the anticonvulsant steroids had greater in vitro potencies than clonazepam, they were less potent in vivo, and they had lower protective indices.