ABSTRACT
Benzodiazepines are generally regarded as positive allosteric modulators of cerebral GABAA receptors, whereby they promote neuronal chloride influx, resulting in reduced propensity of neurons to fire, especially in response to anxiety- or seizure-like stimuli. Despite the therapeutic relevance of this target, benzodiazepines and their natural congeners may also interact with peripheral binding sites affecting mitochondrial function, cholesterol transport, immune responses, oxidative stress, and cell demise. Thus, occupancy of these sites by therapeutic benzodiazepines results in peripheral and, eventually, adverse effects that may play a pivotal role especially after long-term benzodiazepine use and withdrawal.
