2021/06/01 by Silvia Diviccaro, Lucia Cioffi, Eva Falvo +2
Chemistry · Neuroscience · Pharmacology, Toxicology and Pharmaceutics · #Bioactive Compounds and Antitumor Agents #Neuroscience and Neuropharmacology Research #Synthesis and pharmacology of benzodiazepine derivatives
paper · pdf · doi:10.1111/jne.12996
openalex publication_date 2021/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Allopregnanolone, a 3α,5α-progesterone metabolite, acts as a potent allosteric modulator of the γ-aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex-dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues.