Abstract
We examined effects of selective M 1 antagonists on hypercapnic and hypoxic ventilatory responses in 17 healthy human volunteers. Subjects were intravenously treated with placebo, pirenzepine (10 mg) and biperiden lactate (4 mg) on three separate days in a randomized double-blind design. Ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia were studied after the drug administration. There were no statistically significant differences in the mean ΔV̇ e/Δ Pet CO 2 or ΔV̇ e/ΔSa O 2 among the three treatments. However, the ΔV̇ e/Δ Pet CO 2 with placebo negatively correlated with the difference in ΔV̇ e/Δ Pet CO 2 between the biperiden and placebo studies (r = −0.65, P < 0.01), but not with that between the pirenzepine and placebo studies. On the other hand, the V̇ e/ΔSa O 2 with placebo negatively correlated with the difference in V̇ e/ΔSa O 2 between the pirenzepine and placebo studies (r = −0.79, P < 0.001), but not with that between the biperiden and placebo studies. These data suggest the possible involvement of M 1 cholinergic receptors in the central CO 2 and peripheral O 2 sensing mechanisms in humans, although the degree of its involvement is not consistent among subjects. These findings may explain the interindividual variation in the control of breathing in humans.
Published Version
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