Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders

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.