Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder

Background: Panic attacks can be induced in persons with panic disorder by inhalation of carbon dioxide. Hypercapnia also elicits a reflex hyperventil ation, which is controlled in part by cholinergic mechanisms. This study in vestigated whether the exaggerated response to car bon dioxide in panic dis order (PD) can be modulated by antagonists of muscarinic cholinergic recept ors. Methods: Twelve patients with PD received biperiden hydrochloride (a muscar inic antagonist that crosses the blood-brain barrier), pirenzepine hydrochl oride (a muscarinic antagonist that does not cross the blood-brain barrier) , or placebo 2 hours before a 35% carbon dioxide-65% oxygen respiratory cha llenge (vs air as a placebo) on 3 separate days, in a double-blind, random crossover design. Results: According to patients' self-ratings of subjective anxiety, inhalat ion of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo. After biperiden tre atment, however, hypercapnia elicited a response profile similar to that el icited by air, whereby subjective anxiety remained similar to preinhalation levels. Conclusions: Consistent with the hypothesis of the study, a centrally activ e muscarinic antagonist can block the response to carbon dioxide commonly o bserved in subjects with PD.