Pharmacology of endogenous neuroactive steroids

Critical Reviews in Neurobiology
Doodipala Samba Reddy

Abstract

Neuroactive steroids are potent endogenous neuromodulators with rapid actions in the central nervous system. Neuroactive steroids have been claimed to have specific physiological roles in normal or pathological brain function. This article reviews the emerging evidence that progesterone-, deoxycorticosterone-, and testosterone-derived endogenous neuroactive steroids play an important role in the modulation of neural excitability and brain function. Neuroactive steroids such as allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC) are extremely potent positive allosteric modulators of GABAA receptors with sedative, anxiolytic, and anticonvulsant properties. The sulfated neuroactive steroids pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS), which are negative GABAA receptor modulators, induce anxiogenic and proconvulsant effects. Thus, natural fluctuations in neuroactive steroid levels during the menstrual cycle and stress could affect several nervous system functions. There is strong evidence that allopregnanolone and THDOC are involved in the pathophysiology of premenstrual syndrome, catamenial epilepsy, major depression, and stress-sensitive brain disorders. Neuroactive steroids PS and DHEAS have b...Continue Reading

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