Allopregnanolone: An overview on its synthesis and effects

Allopregnanolone, a 3 alpha,5 alpha-progesterone metabolite, acts as a potent allosteric modulator of the gamma-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.

Automated summary

The review discusses the synthesis of allopregnanolone in the nervous system, its physiological and neuroprotective effects, as well as its sex-dimorphic nature. Allopregnanolone's low bioavailability and extensive hepatic metabolism limit its use as a drug, leading to proposals for synthetic analogues or alternative therapeutic strategies to increase its levels.