Modulation by Muscarinic Antagonists of the Response to Carbon Dioxide Challenge in Panic Disorder
Abstract
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.
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Possible explanations for the weaker anti-panic properties of fluvoxamine and imipramine are that fluvoxamine has the lowest in vitro anticholinergic effects and imipramine has the weakest effect on the serotonergic system.
“Possible explanations are that fluvoxamine has the lowest in vitro anticholinergic effects, which are thought to be involved in respiratory aspects of anti-panic activity [50], whereas imipramine has the weakest effect on the serotonergic system, which plays a crucial role in the pathophysiology of panic–respiration connection [37, 51].”
From Management of Treatment-Resistant Panic Disorder (2017) · cites this paper as [50]
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Self-citation
- Authors
- Battaglia, M., Bertella, S., Ogliari, A., Bellodi, L., & Smeraldi, E.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- IRCCS Eugenio Medea (IT)
- IRCCS Ospedale San Raffaele (IT)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2001-02-01
- Volume
- 58
- Issue
- 2
- Pages
- 114
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2155886819
- Cited by
- 41
- References
- 38
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 1 · 2020: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- panic disorder, carbon dioxide challenge, hypercapnia, antimuscarinic agents, biperiden, pirenzepine, cholinergic mechanisms, anxiety, blood-brain barrier
- MeSH terms
- Adult, Biperiden, Carbon Dioxide, Female, Humans, Hypercapnia, Hyperventilation, Male, Pirenzepine, Placebos, Receptors, Cholinergic, Severity of Illness Index, Panic Disorder, Age of Onset, Cross-Over Studies, Muscarinic Antagonists
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