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Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders

Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders,10.1016/S0165-6147(99)01318-8,Trends in Pharmacological Scie

Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders   (Citations: 100)
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Neuroactive steroids are a novel class of positive allosteric modulators of the GABAA receptor. Although neuroactive steroids are endogenous neuronal modulators, synthetic entities with improved oral bioavailability have recently been developed. These compounds demonstrate efficacy as anticonvulsants against a range of convulsant stimuli and demonstrate anti-epileptogenic activity in a kindling model of epilepsy. Efficacy has also been reported in preclinical models of anxiety, insomnia, migraine and drug dependence. Clinical evidence to date is generally supportive of these findings and indicates that neuroactive steroids are generally well tolerated. Taken as a whole, current data suggest that neuroactive steroids could have a future role in clinical practice. In this article, Maciej Gasior, Richard Carter and Jeffrey Witkin review preclinical and clinical evidence that forms the basis for predicting the potential therapeutic application of neuroactive steroids.
Journal: Trends in Pharmacological Sciences - TRENDS PHARMACOL SCI , vol. 20, no. 3, pp. 107-112, 1999
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    • ...For example, ALLO treatment decreased cocaine- (Anker et al. 2009) and yohimbine- (Anker and Carroll 2010a) primed reinstatement of cocaine seeking in female rats and blocked acute convulsions (Gasior et al. 1999) and kindling (Kaminski et al. 2003) following the administration of a large dose of cocaine in male mice...

    Justin J. Ankeret al. Differential effects of allopregnanolone on the escalation of cocaine ...

    • ...As a potent positive allosteric modulator of GABAA receptors (Schumacher and McEwen 1989; for reviews, see Lambert et al. 1995; Gasior et al. 1999), ALLO may indirectly modulate dopamine in both the nucleus accumbens and ventral tegmental areas thereby affecting cocaineseeking behavior...

    Justin J. Ankeret al. Effects of allopregnanolone on the reinstatement of cocaine-seeking be...

    • ... As exogenous drugs, neuroactive steroids are potential anticonvulsants, anxiolytics and anesthetic...

    Lawrence N Eisenmanet al. Anticonvulsant and anesthetic effects of a fluorescent neurosteroid an...

    • ...Apart from their anesthetic, sedative–hypnotic, and anticonvulsant profile, GABAA-receptor-active 3α-reduced neurosteroids have demonstrated robust efficacy in preclinical models of anxiety, migraine, insomnia, and drug dependence (Gasior et al. 1999; Mellon and Griffin 2002; Rupprecht et al. 1998, 2001; Zorumski et al. 2000)...
    • ...Numerous excellent reviews have offered an exhaustive picture of the biosynthesis, putative mechanisms of action, pharmacological profiles, physiological roles, neuropsychiatric effects, and potential clinical applications of 3αreduced and other neurosteroids (van Broekhoven and Verkes 2003; Dubrovsky 2000, 2005; Gasior et al. 1999; Griffin et al. 2001; Mellon and Griffin 2002; Pisu and Serra 2004; Reddy 2002, 2003a,b; Rupprecht 2003; ...

    Veska Uzunovaet al. Relevance of endogenous 3α-reduced neurosteroids to depression and ant...

    • ... In addition to inducing anaesthesia, lower doses of steroids produced anxiolytic, analgesic, anticonvulsant, sedative and hypnotic effect...

    Delia Belelliet al. Neurosteroids: endogenous regulators of the GABAA receptor

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