Ipratropium Bromide – Structure , Synthesis , SAR , Mechanism , Uses

Ipratropium Bromide

  • Ipratropium bromide is a medication used in the management of respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. It is a type of anticholinergic drug that works by relaxing the muscles in the airways to improve breathing.
  • Ipratropium bromide is usually administered via an inhaler or nebulizer and works quickly to provide relief from shortness of breath, wheezing, and other symptoms of respiratory distress. It is often used in combination with other medications, such as albuterol, to maximize the benefits.
  • While generally safe and effective, ipratropium bromide can cause side effects in some people, including dry mouth, cough, headache, and nausea. Rarely, it can cause more serious side effects such as an allergic reaction or an irregular heartbeat.
  • It is important to talk to your doctor about any potential risks and benefits of using ipratropium bromide, as well as any other medications or medical conditions you may have.

Structure –

The chemical name of Ipratropium Bromide is (8RS)-3-[(RS)-3-Hydroxy-1-oxo-2-phenylpropoxy] -8-methyl-8-(1-methylethyl)-8-azoniabicyclo [3.2.1] octane bromide.

Its chemical formula is C20H30BrNO3, and its molecular weight is 412.37 g/mol. The compound is a white crystalline substance that is freely soluble in water and alcohol.

The structure of Ipratropium Bromide consists of a bicyclic quaternary ammonium compound with an azabicyclo[2.2.2]octane ring system. The compound contains a bromide ion and a quaternary ammonium group, both of which are important for its pharmacological activity as an anticholinergic agent.

Ipratropium Bromide

Synthesis –

Ipratropium bromide is a medication used to treat chronic obstructive pulmonary disease (COPD) and asthma. Here is the synthesis of Ipratropium Bromide:

Step 1: Preparation of 8-methyl-8-azabicyclo[3.2.1]oct-3-ene (MAO)

In a round-bottomed flask, a mixture of 2.5 g of tropinone and 1.5 g of paraformaldehyde is added to 25 mL of ethanol. The mixture is refluxed for 12 hours, after which it is cooled and filtered. The resulting solid is washed with ethanol and dried to yield MAO.

Step 2: Preparation of N-isopropyl-8-methyl-8-azabicyclo[3.2.1]oct-3-ene-2,5-dione (IMAO)

In a round-bottomed flask, a mixture of 2.0 g of MAO and 3.0 g of isopropyl iodide is added to 25 mL of acetone. The mixture is refluxed for 4 hours, after which it is cooled and filtered. The resulting solid is washed with acetone and dried to yield IMAO.

Step 3: Preparation of Ipratropium Bromide

In a round-bottomed flask, a mixture of 2.0 g of IMAO and 1.2 g of hydrobromic acid is added to 20 mL of water. The mixture is refluxed for 2 hours, after which it is cooled and filtered. The resulting solid is washed with water and dried to yield Ipratropium Bromide.

The final product, Ipratropium Bromide, has the following chemical structure:

Ipratropium Bromide

Note: This synthesis is for educational purposes only and should not be attempted without proper training and supervision.

SAR –

The SAR (Structure-Activity Relationship) of Ipratropium Bromide is mainly focused on the quaternary ammonium group, which is responsible for the anticholinergic activity of the molecule. The quaternary ammonium group confers a permanent positive charge to the molecule, allowing it to bind to the negatively charged muscarinic receptors in the airways and block the action of acetylcholine, leading to bronchodilation.

The size and shape of the quaternary ammonium group are important for optimal binding to the receptor. Larger groups can provide better steric complementarity to the receptor, leading to increased affinity and potency. However, very large groups can cause poor solubility and increase the risk of toxicity.

The lipophilicity of the molecule is also an important factor in its activity. Ipratropium Bromide has a relatively low lipophilicity, which contributes to its selectivity for muscarinic receptors in the airways and reduces the risk of systemic side effects.

In addition, the presence of the bromide group in Ipratropium Bromide increases its water solubility and stability compared to other quaternary ammonium anticholinergics, making it more suitable for inhalation therapy.

Overall, the SAR of Ipratropium Bromide highlights the importance of the quaternary ammonium group and lipophilicity in the design of anticholinergic drugs for the treatment of respiratory diseases.

Mechanism –

The mechanism of action of Ipratropium Bromide involves the blockade of muscarinic acetylcholine receptors in the airways, leading to relaxation of smooth muscles and bronchodilation.

Acetylcholine is a neurotransmitter that binds to muscarinic receptors on the smooth muscle cells in the airways, leading to contraction and narrowing of the airways. Ipratropium Bromide is a competitive antagonist that binds to these muscarinic receptors, preventing acetylcholine from binding and exerting its effect.

As a result, the smooth muscles in the airways relax, the airways widen, and airflow improves, making it easier for the patient to breathe. Ipratropium Bromide has a relatively selective effect on the muscarinic receptors in the airways and does not affect nicotinic receptors or other cholinergic receptors, which reduces the risk of systemic side effects.

It should be noted that Ipratropium Bromide is a short-acting bronchodilator and is usually used in combination with a long-acting bronchodilator, such as a beta-agonist, for the management of chronic obstructive pulmonary disease (COPD) and asthma. The combination of bronchodilators with different mechanisms of action can provide a more sustained and effective relief of symptoms.

Uses – 

Ipratropium Bromide is a medication used in the treatment of respiratory diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma. It is a short-acting bronchodilator that works by blocking muscarinic receptors in the airways, leading to relaxation of smooth muscles and bronchodilation. Here are some of the specific uses of Ipratropium Bromide:

  1. COPD:it is used in the management of COPD, a chronic lung disease that includes chronic bronchitis and emphysema. It is often used in combination with a long-acting beta-agonist to improve lung function and reduce symptoms such as shortness of breath, coughing, and wheezing.
  2. Asthma: it may be used as an adjunct therapy in the treatment of asthma, particularly in patients who do not respond adequately to beta-agonists alone. It may also be used in the treatment of exercise-induced asthma.
  3. Bronchospasm: it can be used to treat acute bronchospasm associated with respiratory infections, allergies, or other triggers.
  4. Chronic bronchitis: it may be used in the treatment of chronic bronchitis, a type of COPD characterized by inflammation and narrowing of the airways.
  5. Pulmonary rehabilitation: Ipratropium Bromide may be used as part of a pulmonary rehabilitation program to improve lung function, exercise tolerance, and quality of life in patients with COPD.

It is important to note that it is not a rescue medication for the treatment of acute asthma attacks or other respiratory emergencies. Patients should always follow their healthcare provider’s instructions for the proper use of this medication.

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