A new look at the 5α-reductase inhibitor finasteride

Deborah (Deb) Finn, Amy S. Beadles-Bohling, Ethan H. Beckley, Matthew Ford, Katherine R. Gililland, Rebecca E. Gorin-Meyer, Kristine Wiren

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Finasteride is the first 5α-reductase inhibitor that received clinical approval for the treatment of human benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss). These clinical applications are based on the ability of finasteride to inhibit the Type II isoform of the 5α-reductase enzyme, which is the predominant form in human prostate and hair follicles, and the concomitant reduction of testosterone to dihydrotestosterone (DHT). In addition to catalyzing the rate-limiting step in the reduction of testosterone, both isoforms of the 5α-reductase enzyme are responsible for the reduction of progesterone and deoxycorticosterone to dihydroprogesterone (DHP) and dihydrodeoxycorticosterone (DHDOC), respectively. Recent preclinical data indicate that the subsequent 3α-reduction of DHT, DHP and DHDOC produces steroid metabolites with rapid non-genomic effects on brain function and behavior, primarily via an enhancement of γ-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Consistent with their ability to enhance the action of GABA at GABAA receptors, these steroid derivatives (termed neuroactive steroids) possess anticonvulsant, antidepressant and anxiolytic effects in addition to altering aspects of sexual- and alcohol-related behaviors. Thus, finasteride, which inhibits both isoforms of 5α-reductase in rodents, has been used as a tool to manipulate neuroactive steroid levels and determine the impact on behavior. Results of some preclinical studies and clinical observations with finasteride are described in this review article. The data suggest that endogenous neuroactive steroid levels may be inversely related to symptoms of premenstrual and postpartum dysphoric disorder, catamenial epilepsy, depression, and alcohol withdrawal.

Original languageEnglish (US)
Pages (from-to)53-76
Number of pages24
JournalCNS Drug Reviews
Volume12
Issue number1
DOIs
StatePublished - Mar 2006

Fingerprint

Finasteride
Oxidoreductases
Steroids
20-alpha-Dihydroprogesterone
Protein Isoforms
Aptitude
Dihydrotestosterone
Alopecia
gamma-Aminobutyric Acid
Testosterone
Alcohols
Aminobutyrates
Desoxycorticosterone
Menstruation
Hair Follicle
Anti-Anxiety Agents
Prostatic Hyperplasia
GABA-A Receptors
Enzymes
Synaptic Transmission

Keywords

  • Alcohol withdrawal
  • Allopregnanolone
  • Depression
  • Epilepsy
  • Finasteride
  • Neuroactive steroids
  • Seizure susceptibility
  • Sexual behavior

ASJC Scopus subject areas

  • Pharmacology
  • Neuropsychology and Physiological Psychology

Cite this

Finn, D. D., Beadles-Bohling, A. S., Beckley, E. H., Ford, M., Gililland, K. R., Gorin-Meyer, R. E., & Wiren, K. (2006). A new look at the 5α-reductase inhibitor finasteride. CNS Drug Reviews, 12(1), 53-76. https://doi.org/10.1111/j.1527-3458.2006.00053.x

A new look at the 5α-reductase inhibitor finasteride. / Finn, Deborah (Deb); Beadles-Bohling, Amy S.; Beckley, Ethan H.; Ford, Matthew; Gililland, Katherine R.; Gorin-Meyer, Rebecca E.; Wiren, Kristine.

In: CNS Drug Reviews, Vol. 12, No. 1, 03.2006, p. 53-76.

Research output: Contribution to journalArticle

Finn, DD, Beadles-Bohling, AS, Beckley, EH, Ford, M, Gililland, KR, Gorin-Meyer, RE & Wiren, K 2006, 'A new look at the 5α-reductase inhibitor finasteride', CNS Drug Reviews, vol. 12, no. 1, pp. 53-76. https://doi.org/10.1111/j.1527-3458.2006.00053.x
Finn DD, Beadles-Bohling AS, Beckley EH, Ford M, Gililland KR, Gorin-Meyer RE et al. A new look at the 5α-reductase inhibitor finasteride. CNS Drug Reviews. 2006 Mar;12(1):53-76. https://doi.org/10.1111/j.1527-3458.2006.00053.x
Finn, Deborah (Deb) ; Beadles-Bohling, Amy S. ; Beckley, Ethan H. ; Ford, Matthew ; Gililland, Katherine R. ; Gorin-Meyer, Rebecca E. ; Wiren, Kristine. / A new look at the 5α-reductase inhibitor finasteride. In: CNS Drug Reviews. 2006 ; Vol. 12, No. 1. pp. 53-76.
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