Dose response of inhaled gallopamil (D600), a calcium channel blocker, in attenuating airway reactivity to methacholine and exercise

Massey, Kenneth L.; Hill, Malcolm; Harman, Eloise; Rutledge, David R.; Ahrens, Richard C.; Hendeles, Leslie

doi:10.1016/0091-6749(88)90950-5

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…Massey et al [23] studied the effects of inhaled gallopamil on methacholineinduced bronchoconstriction and observed partial inhibi tion in all 11 subjects studied. In our study, gallopamil par tially attenuated the methacholine response in only 3 sub jects and was ineffective in 5 others.…”

Section: Discussionmentioning

confidence: 99%

“…Gallopamil has been shown to inhibit antigen and exer cise-induced bronchoconstriction in humans [21,23], how ever, its comparative effects on agonist-induced broncho constriction have not been well studied. Massey et al [23] studied the effects of inhaled gallopamil on methacholineinduced bronchoconstriction and observed partial inhibi tion in all 11 subjects studied.…”

Section: Discussionmentioning

confidence: 99%

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Modification of Histamine- and Methacholine-Induced Bronchoconstriction by Calcium Antagonist Gallopamil in Asthmatics

Ahmed

Danta

1992

Respiration

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We studied the comparative modification of histamine- and methacholine-induced bronchoconstriction by a calcium antagonist, gallopamil, in 8 subjects with bronchial asthma. Dose-response curves to aerosolized methacholine or histamine were performed, without and following pretreatment with inhaled gallopamil (10 mg), on 6 different experiment days to determine the cumulative provocative dose (PD₅₀) of each agonist in breath units which caused a 50% decrease in specific airway conductance (SGaw). Baseline values of SGaw were similar on different experiment days and gallopamil had no significant effect on SGaw. PD₅₀ values for histamine on control and placebo days were 6.8 ± 2.8 and 5.2 ± 2.8 breath units (mean ± SE), respectively. Pretreatment with gallopamil increased histamine PD₅₀ to 19.8 ± 7.5 breath units, which was significantly greater than on control and placebo days (p < 0.01). PD₅₀ values for methacholine on control and placebo days were 9.5 ± 5.6 and 8.8 ± 5.8 breath units, respectively. Gallopamil pretreatment had no significant effect on methacholine-induced bronchoconstriction; methacholine PD₅₀ increased to 13.4 ± 5.5 breath units (p = NS). The mean dose ratio (ratio of PD₅₀ for the agonist in the presence and absence of gallopamil) for histamine was 6.9, which was 3.7-fold higher than the dose ratio of 1.9 methacholine in the same subjects. These data suggest that gallopamil causes greater inhibition of histamine- versus methacholine-induced bronchoconstriction. This suggests that calcium influx in airway smooth muscle through voltage-dependent channels primarily occurs in response to histamine and not to methacholine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modification of Histamine- and Methacholine-Induced Bronchoconstriction by Calcium Antagonist Gallopamil in Asthmatics

Ahmed

Danta

1992

Respiration

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“…Altered regulation of transmembrane and intracellular calcium concentrations in mast cells and airway smooth muscle may play a role in the pathogenesis of asthma [1–3]. Many studies have documented that single doses of calcium channel blockers attenuate airway responsiveness to exercise [4–6], and cold air [7, 8] in subjects with asthma. In contrast, there are conflicting results for attenuation of airway responsiveness to methacholine [6, 9, 10], histamine [9, 11], and allergen [12, 13].…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have documented that single doses of calcium channel blockers attenuate airway responsiveness to exercise [4±6], and cold air [7,8] in subjects with asthma. In contrast, there are con¯icting results for attenuation of airway responsiveness to methacholine [6,9,10], histamine [9,11], and allergen [12,13]. In one study, graded doses of nebulized diltiazem had no effect on airway responsiveness to exercise or methacholine [14], whereas a similar study design indicated that inhaled gallopamil (methoxyverapamil) attenuated both [6].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, there are con¯icting results for attenuation of airway responsiveness to methacholine [6,9,10], histamine [9,11], and allergen [12,13]. In one study, graded doses of nebulized diltiazem had no effect on airway responsiveness to exercise or methacholine [14], whereas a similar study design indicated that inhaled gallopamil (methoxyverapamil) attenuated both [6]. Nifedipine may have a bronchodilator effect [15±17], as well as enhancing the bronchodilator effects of b 2 -adrenoceptor selective agonists [18,19].…”

Section: Introductionmentioning

confidence: 99%

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