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 hyperventilation, which is controlled in part by cholinergic mechanisms. This study investigated whether the exaggerated response to carbon dioxide in panic disorder (PD) can be modulated by antagonists of muscarinic cholinergic receptors.


METHODS
Twelve patients with PD received biperiden hydrochloride (a muscarinic antagonist that crosses the blood-brain barrier), pirenzepine hydrochloride (a muscarinic antagonist that does not cross the blood-brain barrier), or placebo 2 hours before a 35% carbon dioxide-65% oxygen respiratory challenge (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, inhalation of the carbon dioxide/oxygen mixture provoked a significant and intense response after treatment with pirenzepine and placebo. After biperiden treatment, however, hypercapnia elicited a response profile similar to that elicited by air, whereby subjective anxiety remained similar to preinhalation levels.


CONCLUSIONS
Consistent with the hypothesis of the study, a centrally active muscarinic antagonist can block the response to carbon dioxide commonly observed in subjects with PD.
Battaglia
M
M
Department of Psychology, University Vita-Salute San Raffaele, Milan, Italy. marco.battaglia@hsr.it
Bertella
S
S
Ogliari
A
A
Bellodi
L
L
Smeraldi
E
E
D000328:Adult; D017668:Age of Onset; D001712:Biperiden / Q000494:pharmacology*; D002245:Carbon Dioxide; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000139:chemically induced* / Q000517:prevention & control*; D006985:Hyperventilation / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D016584:Panic Disorder / Q000139:chemically induced / Q000175:diagnosis* / Q000517:prevention & control*; D010890:Pirenzepine / Q000494:pharmacology*; D010919:Placebos; D011950:Receptors, Cholinergic / Q000187:drug effects; D012720:Severity of Illness Index
D018727:Muscarinic Antagonists; D010919:Placebos; D011950:Receptors, Cholinergic; D001712:Biperiden; D002245:Carbon Dioxide; D010890:Pirenzepine