Neuroactive steroid

Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy. Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, neuroactive steroid refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy. Based on differences in activity and structure, neurosteroids can be broadly categorized into several different major groupings. These neurosteroids exert inhibitory actions on neurotransmission. They act as positive allosteric modulators of the GABAA receptor (especially δ subunit-containing isoforms), and possess, in no particular order, antidepressant, anxiolytic, stress-reducing, rewarding, prosocial, antiaggressive, prosexual, sedative, pro-sleep, cognitive and memory-impairing, analgesic, anesthetic, anticonvulsant, neuroprotective, and neurogenic effects. Major examples include tetrahydrodeoxycorticosterone (THDOC), the androstane 3α-androstanediol, the cholestane cholesterol and the pregnanes pregnanolone (eltanolone), allopregnanolone (brexanolone). These neurosteroids have excitatory effects on neurotransmission. They act as potent negative allosteric modulators of the GABAA receptor, weak positive allosteric modulators of the NMDA receptor, and/or agonists of the σ1 receptor, and mostly have antidepressant, anxiogenic, cognitive and memory-enhancing, convulsant, neuroprotective, and neurogenic effects. Major examples include the pregnanes pregnenolone sulfate (PS), epipregnanolone, and isopregnanolone (sepranolone), the androstanes dehydroepiandrosterone (DHEA; prasterone), and dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate), and the cholestane 24(S)-hydroxycholesterol (NMDA receptor-selective; very potent). Pheromones are neurosteroids that influence brain activity, notably hypothalamic function, via activation of vomeronasal receptor cells. They include the androstanes androstadienol, androstadienone, androstenol, and androstenone and the estrane estratetraenol. Certain other endogenous steroids, such as pregnenolone, progesterone, estradiol, and corticosterone are also neurosteroids. However, unlike those listed above, these neurosteroids do not modulate the GABAA or NMDA receptors, and instead affect various other cell surface receptors and non-genomic targets. Also, many endogenous steroids, including pregnenolone, progesterone, corticosterone, deoxycorticosterone, DHEA, and testosterone, are metabolized into (other) neurosteroids, effectively functioning as so-called proneurosteroids.