An M1-selective muscarinic receptor antagonist telenzepine improves lung function in patients with chronic obstructive bronchitis.
The effect of an M1-selective muscarinic receptor antagonist telenzepine on lung function was investigated in 18 patients with chronic obstructive bronchitis in a double blind, placebo-controlled, randomized crossover study. FEV1, FEF50, PEF and FVC were measured every 0.5 h up to 2 h, then every 1 h up to 6 h after administration of a single, oral dose of 5 mg in the morning. Compared with placebo, telenzepine increased (time average over 6 hours; median and 68%-range): 1) FEV1 from 1.46 (0.81, 2.06) to 1.67 (1.06, 2.40) l, p less than 0.01; 2) PEF from 3.58 (2.33, 4.55) to 3.88 (3.10, 5.07) l/s, p less than 0.01; 3) FEF50 from 0.93 (0.45, 1.58) to 1.17 (0.67, 1.90) l/s, p less than 0.001. Whereas the median increase in FEV1 15 min after 2 puffs of salbutamol was 20% (range 15 to 74%), FEV1 improved by 32% (range -15 to 130%) at the time of maximum difference between placebo and telenzepine. The heart rate did not change. We conclude that in patients with chronic obstructive bronchitis substantial improvement of lung function parameters can be achieved by an M1-receptor antagonist. It is possible that with the dose administered direct actions on muscarinic receptors on the smooth muscle (M3) contribute to the observed bronchodilatation. The unchanged heart rate indicates little effect on cardiac M2-receptors.
Cazzola
M
M
Department of Pulmonary Medicine, A. Cardarelli Hospital, Naples, Italy.
D'Amato
G
G
Guidetti
E
E
Staudinger
H
H
Steinijans
V W
VW
Kilian
U
U
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001699:Biometry; D001991:Bronchitis / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists; D010276:Parasympatholytics / Q000627:therapeutic use*; D010865:Pilot Projects; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012129:Respiratory Function Tests
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; C046338:telenzepine; D010890:Pirenzepine