From the FDA Drug Label
Anticholinergics prevent the increases in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) that are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. The FDA drug label does not specify which muscarinic receptors ipratropium acts on, only that it antagonizes the action of acetylcholine at the muscarinic receptor on bronchial smooth muscle 1.
From the Research
Ipratropium acts as a non-selective muscarinic antagonist, blocking M1, M2, and M3 receptors, with its primary therapeutic effects in the airways coming from M3 receptor antagonism. This is based on the study by 2, which highlights the role of muscarinic receptors in regulating bronchial tone in chronic obstructive pulmonary disease (COPD). The study explains that M3 receptors on airway smooth muscle cells and glands mediate bronchoconstriction and mucus secretion, making them a key target for ipratropium's therapeutic effects.
Some key points about ipratropium's mechanism of action include:
- It blocks M1, M2, and M3 receptors, but its primary effects come from M3 receptor antagonism
- M3 receptors are responsible for mediating bronchoconstriction and mucus secretion in the airways
- Ipratropium's non-selective muscarinic antagonism reduces bronchial tone and mucus secretion, making it an effective treatment for respiratory conditions like COPD and asthma
- The medication has limited systemic effects due to its poor absorption when administered via inhalation, and its quaternary ammonium structure restricts its ability to cross the blood-brain barrier
It's worth noting that while ipratropium blocks all muscarinic subtypes, its clinical benefit comes mainly from M3 receptor antagonism. This is supported by the study by 3, which found that female patients with mild to moderate COPD had a greater response to ipratropium than male patients, and that this response was particularly notable in non-obese females. The study also found that female lungs had greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs, which may explain the greater response to ipratropium in female patients. Overall, ipratropium's non-selective muscarinic antagonism, particularly its blockade of M3 receptors, makes it an effective treatment for respiratory conditions like COPD and asthma.