Repurposing steroidogenesis inhibitors for the therapy of neuropsychiatric disorders: Promises and caveats

Frau, Roberto; Bortolato, Marco

doi:10.1016/j.neuropharm.2018.05.013

Cited by 11 publications

(7 citation statements)

References 142 publications

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“…For instance, finasteride treatment exerts neuroprotective effects in ischemic brain injury induced in aged male rats (Tanaka et al, 2019), while dutasteride is protective in an experimental model of PD (Litim et al, 2015(Litim et al, , 2017. In addition, several observations suggest that these 5α-R inhibitors have therapeutic efficacy in behavioral disorders and specifically those associated with dopaminergic hyperfunction, such as Tourette syndrome and dyskinetic manifestations (Bortolato et al, 2008;Fanni et al, 2019;Frau and Bortolato, 2019). Finally, dutasteride reduces subsequent alcohol consumption in subjects classified as heavy drinkers (Covault et al, 2014).…”

Section: α-Reductase Inhibitorsmentioning

confidence: 99%

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Giatti

Diviccaro

Serafini

et al. 2020

Frontiers in Neuroendocrinology

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The nervous system, in addition to be a target for steroid hormones, is the source of a variety of neuroactive steroids, which are synthesized and metabolized by neurons and glial cells. Recent evidence indicates that the expression of neurosteroidogenic proteins and enzymes and the levels of neuroactive steroids are different in the nervous system of males and females. We here summarized the state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules. In addition, we discuss the consequences of sex differences in neurosteroidogenesis for the function of the nervous system under healthy and pathological conditions and the implications of neuroactive steroids and neurosteroidogenesis for the development of sex-specific therapeutic interventions.

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Section: α-Reductase Inhibitorsmentioning

confidence: 99%

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Giatti

Diviccaro

Serafini

et al. 2020

Frontiers in Neuroendocrinology

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“…Although it is considered a well-tolerated and relatively safe drug, there is evidence of sexual disfunction in 3.4 to 15.8 percent of men. A rare but serious side effect known as post-finasteride syndrome (PFS) has also been reported (81)(82)(83). PFS prevalence is unclear but it manifests as a range of persistent physical and neuropsychiatric disorders such as depression and anxiety that develop during or after discontinuation of finasteride use.…”

Section: Discussionmentioning

confidence: 99%

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

Bossé¹,

Cadeddu²,

Floris³

et al. 2021

Journal of Clinical Investigation

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Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.

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“…Although it is considered a well-tolerated and relatively safe drug, there is evidence of sexual disfunction in 3.4 to 15.8 percent of men. A rare but serious side effect known as post-finasteride syndrome (PFS) has also been reported [84][85][86] . PFS prevalence is unclear but it manifests as a range of persistent physical and neuropsychiatric disorders such as depression and anxiety that develop during or after discontinuation of finasteride use.…”

Section: Discussionmentioning

confidence: 99%

The 5α-reductase inhibitor finasteride reduces opioid self-administration

Bossé

Cadeddu

Floris

et al. 2020

Preprint

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Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel potential treatments for OUD, we screened a targeted selection of over 100 drugs, using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride did not interfere with the antinociceptive effect of opioids in rat models of neuropathic pain. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish, in a fashion akin to the effects of finasteride. Our results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new option for this disorder.

show abstract

Repurposing steroidogenesis inhibitors for the therapy of neuropsychiatric disorders: Promises and caveats

Cited by 11 publications

References 142 publications

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

The 5α-reductase inhibitor finasteride reduces opioid self-administration

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