Abstract

The paper presents the structure and functional relationship of beta2-agonists and the beta2-adrenoceptor. The human beta2-adrenoceptor is a member of the 7-transmembrane family of receptors. Most of the actions of the beta2-receptor are mediated through the Gs protein and the cAMP-dependent PKA system. Alternative cAMP-independent pathways affected following beta2-receptor activation have also been described. Beta2-agonists have been used as bronchodilator agents in the treatment of asthma since the development of inhaled isoprenaline preparations in 1961. Over the years, these agents have been markedly improved through the development of short-acting beta2 selective agents followed by long-acting beta2 selective agents with prolonged duration of action. Efforts directed towards improving the pharmacodynamic and pharmacokinetic properties, including the long-acting and selective beta2-adrenoceptor agonists, included two major pathways of modifying the basic structure of the catecholamines, which are described in this paper. The pharmacological activity usually resides in the (R)-enantiomer. The kinetics of beta2-agonist-stimulated bronchodilation in asthma is determined by the differences in the molecular mechanism of beta2-agonists action. Regulation of the beta2-receptor is influenced by its desensitization following exposure to high concentrations of or repeated challenges with agonists, and up-regulation which can be induced by glucocorticoids and thyroid hormones.

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