GABAA Receptor Subtypes: Novel Targets for Novel Medicines
1CNS Integration, NeuroSearch A/S, 2750 Ballerup, Denmark
2Janssen Beerse; University of Antwerp, Antwerp, Belgium
3Lilly UK, Erl Manor, Windlesham, Surrey, UK
GABAA Receptor Subtypes: Novel Targets for Novel Medicines
Description
GABAA receptors are located both synaptically and extrasynaptically and are not only important in mediating inhibitory neurotransmission but also represent an important target for medicines used today, including benzodiazepines, the so-called “Z-drug” hypnotics, etomidate, and propofol. Over the last decade, knowledge from various disciplines, notably molecular biology and pharmacology, has propelled our knowledge on GABAA receptors to a point where this knowledge is now being exploited to develop novel medicines. Experiments using exquisite genetically modified mice and pharmacological tool compounds have enhanced our knowledge of the functional roles of different synaptic GABAA receptors and demonstrated that different effects of benzodiazepines, Z-drug hypnotics, and etomidate are mediated via different GABAA receptor subtypes. This has led to the development of novel subtype selective compounds; some of which have been assessed in early stages of clinical development and shown to differ from existing drugs that target GABAA receptors. In addition, extrasynaptic GABAA receptors are not influenced by the majority of clinically available drugs targeting GABAA receptors and therefore represent underexploited targets. However, basic science knowledge on extrasynaptic GABAA receptors and their purported role in insomnia, female stress disorders, major depression, PTSD, and autism suggest these receptors represent fruitful targets for novel medicines.
In this special issue, we would like authors to submit original research or review article that focus on, but are not restricted to, basic research, drug discovery and drug development efforts within the following three GABAA target fields. Potential topics include, but are not limited to:
- GABAA-α2/α3 selective positive allosteric modulators
- GABAA-α5 selective positive and negative allosteric modulators
- δ-containing GABAA receptors
Before submission authors should carefully read over the journal's Author Guidelines, which are located at http://www.hindawi.com/journals/aps/guidelines.html. Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/ according to the following timetable: