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.

Allopregnanolone: An overview on its synthesis and effects / S. Diviccaro, L. Cioffi, E. Falvo, S. Giatti, R.C. Melcangi. - In: JOURNAL OF NEUROENDOCRINOLOGY. - ISSN 0953-8194. - (2021). [Epub ahead of print] [10.1111/jne.12996]

Allopregnanolone: An overview on its synthesis and effects

S. Diviccaro
Primo
;
L. Cioffi;E. Falvo;S. Giatti;R.C. Melcangi
Ultimo
2021

Abstract

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.
neuroactive steroids; neurodegenerative disorders; progesterone metabolism; psychiatric disorders; sex difference
Settore MED/13 - Endocrinologia
1-giu-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/891023
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