SALMETEROL

Pharmacology

• Greater lipophilicity

• Different mechanism

• Specific binding contributing to 12 hours of duration

• Guinea Pig models

• Significant inhibition in inflammatory mediator release

SALMETEROL

Structural Activity Relationship

Conclusion

• Bulk on nitrogen increases Beta receptor activity

Amino group:

• essential for direct activity

• Must be separated by 2 carbon atoms.

• Meta-hydroxy group replaced by methyl hydroxy gives good Beta 2 receptor selectivity

• First treatment was 100 years ago

• Earlier non selective beta agonists (isoprenaline & epinephrine) were used

• Target identification of beta 2 receptor led to discovery of Salbutamol & later Salmeterol

• The phenyl alkyl side chain is responsible for the long 12 hours of activity

• Binding to exosite and high lipophylicity (different mechanism )

• It's not a first line treatment but preferred as a combination drug

History of Asthma

• Asthma?
• Causes of Asthma: environmental, occupational and genetic
• Triggering Factors: dust, fumes, pollens, pet dander
• Heavy Exercise & Stress

Drugs used:

• Inhaled corticosteroids, ex: flunisolide
• Long acting beta 2 agonist, salmeterol

• Combination inhalers, fluticasone-salmeterol
• Short acting beta2 agonist, salbutamol

Synthesis of Salmeterol

• Asymmetric borane reduction – oxazaborolidine and borane

Target Identification

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(Serevent)

By: Kavya Cukkemane, Akshit Jaiswal, Zacharias Olsen, Aðalbjörg Þorkelsdóttir, Gloria Singla