Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks are reportedly attenuated by effective treatment with antipanic antidepressants in patients with panic disorder, but in healthy volunteers such effects are not well studied.
As glyoxylate is part of the degradation circuit of cholecystokinin, this suggests that this neuropeptide might be directly involved in exposure-induced panic attacks.
Efforts to dissect BPAD have been based on the course of the disorders (BP I versus BP II or rapid cycling), comorbidity pattern (panic attacks, suicide attempts, addiction or hyperactivity), differences between the sexes, and clinical pattern (cycloid and puerperal psychosis).
Experimental results obtained in rat models of panic indicate that serotonin interacts synergistically with endogenous opioids in the dorsal periaqueductal gray through 5-HT1A and μ-opioid receptors to inhibit proximal defense and, supposedly, panic attacks.
Finally, the study also found that participants experienced a perpetuating cycle of dyspnea, anxiety, and fear of breathlessness due to COPD which could lead to more severe dyspnea and even panic attacks.
However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion.