P2-Adrenergic receptor agonists

Inhaled selective p2-adrenergic receptor agonists (albuterol, terbutaline, fenoterol, and bitolterol) have a rapid onset of action and are effective for 3 to 6 hours. Formoterol and salmeterol are longer-acting agents (12 hours) and may prove useful in treating nocturnal symptoms. 

Effective agents may include glucocorticoids, anticholineigic agents, leukotriene-receptor antagonists, and P2-adrenergic receptor agonists. Methylxanthines, such as theophylline, are also useful. 

Albuterol (e.g., Ventolin, Proventil) P2 adrenergic receptor agonist - causes bronchodilation. Drug of choice for treatment of acute asthma symptoms and to prevent exertion-induced asthma. Though promoted as a fte- selective agonists, side effects parallel nonspecific agonists (vasodilation, tachycardia, CNS stimulation, metabolic alterations. Table 2.1). Inhalation preparations have fewer side effects. 

Eickelberg 0, Roth M, Lorx R, et al. Ligand-independent activation of the glucocorticoid receptor by P2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 1999 274 1005-1010. 

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

Some failures will be due to the presence of variants in drug handling. Patients who are rapid acetylators of isoniazid have a slower antituberculous response than slow acetylators (Evans and Clarke, 1961). Asthmatics who do not respond well to (32-agonist bronchodilators may have fewer functioning p2-adrenergic receptors (Drysdale et al., 2000). Variations in the synthesis or structure of the serotonin transporter protein, which is involved in selective reuptake of serotonin by presynaptic neurons, may explain why some patients with depressive disorders respond to selective serotonin reuptake inhibitors and others do not (Steimer et al., 2001). 

Freddolino PL, Kalani MY, Vaidehi N, et al. Predicted 3D structure for the human P2 adrenergic receptor and its binding site for agonists and antagonists. Proc Natl Acad Sci USA 2004 101 2736-2741. 

Kurose H, Isogaya M, Kikkawa H, Nagao T. Domains of (3, and P2 adrenergic receptors to bind subtype selective agonists. Life Sci 1998 62 1513-1517. 

Isogaya M, Sugimoto Y, Tanimura R, et al. Binding pockets of the p,- and p2-adrenergic receptors for subtype-selective agonists. MolPharmacol 1999 56 875-885. 

Kobilka BK. Agonist-induced conformational changes in the p2 adrenergic receptor. J Pept Res 2002 60 317-321. 

Kawahira Y, Sawa Y, Nishimura M, et al. In vivo transfer of a p2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to P-adrenergic agonist. Circulation 1998 98 11262-11267. 

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