ATC Code: R03
The active ingredient of indacaterol maleate is indacaterol (ChEMBL: 1095777) an agonist of the beta-2 adrenergic receptor (Uniprot: P07550, ChEMBL: 210) with measured EC50 of 11nM. Indacaterol exerts its effect through activation of the beta-2 adrenergic receptor, leading to smooth muscle relaxation and a widening of bronchioli in the lungs. Activation of the beta-2 adrenergic receptor stimulates the intracellular adenyl cyclase and increases cAMP levels, which in turn leads to a reduction of the level of calcium ions inside smooth muscle cells. Other long acting beta-adrenoceptor agonists (LABA) such as salmeterol, formoterol and bambuterol entered the market during the 1980s. The duration of action of these earlier compounds is 12 hours, while for indacaterol it is 24 hours.
Multiple crystal structures of the beta-2 adrenergic receptor now exist (PDBe: 2R4R, 2R4S, 2RH1, 3D4S, 3KJ6, 3NY8, 3NY9, 3NYA, 3P0G, 3PDS), a nano-body stabilized structure of the receptor in its activated form is shown below (PDBe: 3p0g).
The USAN stem name -terol indicates that indacaterol is a phenethylamine derivative bronchodilator. Other -terols include salmeterol, formoterol, bambuterol, vilanterol, milveterol and levalbuterol.
Indacaterol's bioavailability after inhalation is (at the recommended dose range of 75-150 µg) is 43-45% and the volume of distribution (Vd) is between 2.36 and 2.56 L.kg-1 and a clearance (CL) of about 20L.hr-1. Steady-state of Indacaterol levels is reached within 12 to 15 days. Plasma protein binding (ppb) of the dosed drug is 95.1-96.2%. Excretion of indacaterol is mainly through the fecal route, either as the parent compound (54% of the dose) or hydroxylated metabolite (23% of the dose).
Indacaterol maleate is administered once daily as an aerosol containing 75-150 µg of active ingredient from a powder inhaler.
Indacaterol maleate was approved by the European commission in 2009 and is marketed in Europe as Onbrez. In the US, indacaterol maleate will be marketed by Novartis under the trade name Arcapta.