subunit-containing GABAA receptors, in contrast to other Z-drugs and to diazepam. Alpidem has very high affinity for the TSPO, while zolpidem has very low affinity for this protein. The affinity of alpidem for the TSPO (also previously known as the ω3 receptor) was once the highest of any drug known. Although benzodiazepines like diazepam are also known to bind to the TSPO, the affinity of alpidem for this protein is at least 3,000-fold higher in comparison. Whereas zolpidem shows hypnotic and sedative effects and is used to treat insomnia, alpidem shows mainly anxiolytic effects and is used to treat anxiety disorders. Alpidem was developed before the widespread use of recombinant GABAA receptors. Hence, its pharmacological profile at the GABAA receptors, including its profile at different subpopulations of these receptors, has never been fully characterized. The pharmacodynamic mechanisms underlying the anxioselective (anxiolytic-selective) profile of alpidem as a GABAA receptor positive allosteric modulator are unclear. In any case, subtype selectivity for different populations of GABAA receptors, partial agonism of the benzodiazepine site of the GABAA receptor, and/or interactions with the TSPO may potentially all be involved. Although anxioselective profiles have been observed for many GABAA receptor positive allosteric modulators in preclinical research, alpidem is the only GABAA receptor positive allosteric modulator for which anxioselective effects have been unambiguously demonstrated in human clinical trials. Ocinaplon has also shown preliminary signs of an anxioselective profile in clinical studies, but development of this agent was discontinued in late-stage trials due to findings of elevated liver enzymes in a small subset of patients. GABAA receptor positive allosteric modulators with selectivity for α2 and α3 subunit-containing GABAA receptors over α1 subunit-containing GABAA receptors, for instance adipiplon, L-838,417, and darigabat—among others, have been and are under investigation as potential anxioselective agents. However, no such drugs have yet completed clinical development or been marketed for medical use. Despite many developmental failures, alpidem serves as a potential proof of concept that anxioselective GABAA receptor positive allosteric modulators may be possible. However, if interactions with the TSPO are key to the anxiolytic effects of alpidem, then this may not actually be the case. Pharmacokinetics Absorption Alpidem is taken via oral administration. The absorption of alpidem is rapid and it reaches peak levels after 1.0 to 2.5hours. Its overall bioavailability is estimated to be approximately 32 to 35%, but no precise value for absolute bioavailability has been determined. Absorption of alpidem as