Effects of M1-selective antimuscarinics on respiratory chemosensitivity in humans

We examined effects of selective M1 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 delta VE/delta PET CO2 or delta VE/delta SaO2 among the three treatments. However, the delta VE/delta PET CO2 with placebo negatively correlated with the difference in delta VE/delta PET CO2 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 delta VE/delta SaO2 with placebo negatively correlated with the difference in delta VE/delta SaO2 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 M1 cholinergic receptors in the central CO2 and peripheral O2 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.