The pharmacological rationale for amiloride nasal spray: potentially a portable and rapid-acting treatment for panic disorder.

Abstract

Panic disorder is among the most common mental disorders, characterised by recurrent, unexpected panic attacks that are highly distressing and further lead to pervasive anxiety about future attacks and maladaptive behavioural changes. Existing pharmacological and psychological treatments often fail to produce lasting improvement, and relapse is common. Neither antidepressants, the current first-line drug treatments, nor benzodiazepines exert their actions sufficiently rapidly to head off panic attacks between the initial indications of panic symptoms and the fully developed panic attack. Therefore, there is a clear need for new pharmacological compounds, particularly those that could be administered at the first warning signs of an impending panic attack, to disrupt its genesis. Here we discuss the acid-sensing ion channel (ASIC) as a therapeutic target and the potential of amiloride, an ASIC antagonist administered via nasal spray, for rapid access to the brain, as a compound with potential to fill this need. We summarise relevant preclinical studies, including a demonstration of nebulised amiloride's ability to normalise responses to carbon dioxide, a panicogenic, brain-acidifying agent. Following existing safety, stability and pharmacokinetic studies, clinical trials are needed to test the efficacy of this compound in individuals with panic disorder and/or recurrent panic attacks.