In vivo human models for the study of anticholinergic drugs

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Presentation transcript:

In vivo human models for the study of anticholinergic drugs Robert M. Naclerio, MD, Fuad M. Baroody, MD Journal of Allergy and Clinical Immunology Volume 95, Issue 5, Pages 1069-1079 (May 1995) DOI: 10.1016/S0091-6749(95)70210-5 Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 1 Schematic drawing of nose and central nervous system. Stimulation of sensory nerves of nasal mucosa initiates a central neuronal reflex that affects both ipsilateral and contralateral nasal cavities via parasympathetic and sympathetic efferent pathways. Sensory stimulation can also lead to axonal reflexes, which affect ipsilateral nasal mucosa. Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

Fig. 2 Dose-response curves of secretion weight after placebo or different doses of ipratropium bromide. BASE, Baseline secretions; SAL, saline challenge; 0.02, 0.06, 0.19, 0.6, 1.7, and 5, doses of methacholine (mg) used for sequential challenges. Error bars are omitted for 21, 42, and 84 μg doses for purposes of clarity. All doses of ipratropium were more effective in inhibiting secretory response to methacholine than was placebo, and 168 μg dose was significantly more effective than other active treatments. (From Baroody FM, Majchel AM, Roecker MM, et al. Ipratropium bromide [Atrovent nasal spray] reduces the nasal response to methacholine. J Allergy Clin Immunol 1992;89:1065-75.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 3 Secretion weights after repetitive challenges with 0.19 mg of methacholine. Time after treatment of each challenge is displayed on abscissa. Data are presented as mean ± SEM of 24 subjects. * = p < 0.05 compared with placebo. The 42 μg dose of ipratropium bromide significantly reduced secretion weights at 15-minute, 30-minute, and 1-hour time points (p < 0.05). the 168 μg dose significantly decreased secretion weights from 15 minutes to 6 hours (p < 0.01). (From Wagenmann M, Baroody FM, Jankowski R, et al. Onset and duration of inhibition of ipratropium nasal spray on methacholine-induced nasal secretions. Clin Exp Allergy 1994;24;288-90). Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 4 Effect of atropine premedication of both sides of nose on ipsilateral (panel A) and contralateral (panel B) responses after stimulation of ipsilateral nasal cavity with histamine. In both panels abscissa represents challenge protocal with the initial saline challenge (Sal) followed by increasing doses of histaming in mg. *p ≤ 0.05 compared with saline challenge within same curve and †p ≤ 0.05 compared with atropine. (From Baroody FM, Wagenmann M, Naclerio RM. A comparison of the secretory response of the nasal mucosa to methacholine and histamine. J Appl Physiol 1993;74:2661-71.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 4 Effect of atropine premedication of both sides of nose on ipsilateral (panel A) and contralateral (panel B) responses after stimulation of ipsilateral nasal cavity with histamine. In both panels abscissa represents challenge protocal with the initial saline challenge (Sal) followed by increasing doses of histaming in mg. *p ≤ 0.05 compared with saline challenge within same curve and †p ≤ 0.05 compared with atropine. (From Baroody FM, Wagenmann M, Naclerio RM. A comparison of the secretory response of the nasal mucosa to methacholine and histamine. J Appl Physiol 1993;74:2661-71.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 5 Effect of topical atropine premedication on ipsilateral changes after antigen challenge. Challenge protocal is shown on abscissa: B, Baseline; Dil, diluent challenge; 3.3, 33.3, and 333.3, doses of antigen used in PNU. Data represent mean ± SEM of nine volunteers. *p ≤ 0.01, **p ≤ 0.05 compared with diluent challenge. †p < 0.05 placebo vs atropine. (From Baroody FM, Ford S, Lichtenstein LM, et al. Physiologic responses and histamine release after nasal antigen challenge: effect of atropine. Am J Respir Crit Care Med 1994;149:1457-65. Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 5 Effect of topical atropine premedication on ipsilateral changes after antigen challenge. Challenge protocal is shown on abscissa: B, Baseline; Dil, diluent challenge; 3.3, 33.3, and 333.3, doses of antigen used in PNU. Data represent mean ± SEM of nine volunteers. *p ≤ 0.01, **p ≤ 0.05 compared with diluent challenge. †p < 0.05 placebo vs atropine. (From Baroody FM, Ford S, Lichtenstein LM, et al. Physiologic responses and histamine release after nasal antigen challenge: effect of atropine. Am J Respir Crit Care Med 1994;149:1457-65. Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 6 Bilateral secretory response after unilateral CDA nasal challenge. A, Both sides treated with placebo; B, atropine ipsilateral and placebo contralateral to challenge; C, placebo ipsilateral and atropine contralateral to challenge. (ipsi, Ipsilateral to CDA challenge; contra, contralateral to CDA challenge; pre dg, pre drug; post dg, post drug. (From Jankowski R, Philip G, Togias A, Naclerio R. Demonstration of bilateral cholinergic secretory response after unilateral nasal cold, dry air challenge. Rhinology 1993;31:97-100.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 6 Bilateral secretory response after unilateral CDA nasal challenge. A, Both sides treated with placebo; B, atropine ipsilateral and placebo contralateral to challenge; C, placebo ipsilateral and atropine contralateral to challenge. (ipsi, Ipsilateral to CDA challenge; contra, contralateral to CDA challenge; pre dg, pre drug; post dg, post drug. (From Jankowski R, Philip G, Togias A, Naclerio R. Demonstration of bilateral cholinergic secretory response after unilateral nasal cold, dry air challenge. Rhinology 1993;31:97-100.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions

FIG. 6 Bilateral secretory response after unilateral CDA nasal challenge. A, Both sides treated with placebo; B, atropine ipsilateral and placebo contralateral to challenge; C, placebo ipsilateral and atropine contralateral to challenge. (ipsi, Ipsilateral to CDA challenge; contra, contralateral to CDA challenge; pre dg, pre drug; post dg, post drug. (From Jankowski R, Philip G, Togias A, Naclerio R. Demonstration of bilateral cholinergic secretory response after unilateral nasal cold, dry air challenge. Rhinology 1993;31:97-100.) Journal of Allergy and Clinical Immunology 1995 95, 1069-1079DOI: (10.1016/S0091-6749(95)70210-5) Copyright © 1995 Mosby, Inc. Terms and Conditions