metyrapone + oxazepam

Metyrapone + oxazepam is a fixed-dose combination drug under development for the treatment of substance use disorders, particularly cocaine dependence and smoking withdrawal. The combination consists of metyrapone, a steroid 11-beta-hydroxylase inhibitor that reduces cortisol synthesis, and oxazepam, a benzodiazepine that acts as a GABA A receptor agonist. Metyrapone inhibits the enzyme responsible for converting 11-deoxycortisol to cortisol in the adrenal cortex, thereby reducing cortisol levels and modulating stress response pathways[1][4]. Oxazepam enhances GABAergic neurotransmission by binding to the benzodiazepine site on the GABA A receptor complex[4]. The rationale behind this combination is to target both stress-related neuroendocrine mechanisms (via metyrapone) and anxiety or craving (via oxazepam), potentially increasing neuroactive steroid levels in brain regions involved in addiction such as the medial prefrontal cortex and amygdala[6]. Developed by Embera NeuroTherapeutics with origins at Louisiana State University, this therapy has reached Phase II/III clinical trials for smoking withdrawal and Phase II for cocaine-related disorders. It remains in preclinical development for eating disorders, gambling disorder, post-traumatic stress disorder (PTSD), and other substance-related conditions[4].

Other names

metyrapone/oxazepam