, 2008,III,2; 58-63

β2–adrenoreceptor agonists. Part II. Pharmacokinetic parameters of the β2-receptor: selectivity, affinity, potency and efficacy. Full and partial agonism. Mechanisms of the receptor desensitization

Agnieszka Kopeć1, Andrzej M. Fal1, 2*

1Katedra i Klinika Chorób Wewnętrznych i Alergologii Akademii Medycznej we Wrocławiu

2Katedra Zdrowia Publicznego Akademii Medycznej we Wrocławiu

There are several pharmacologic parameters that characterize the interaction of a β2-agonist with its receptor. They include amongst other: selectivity, affinity, potency and efficacy. Selectivity describes drug ability to selective binding to the specific structure, e.g. receptor subtype. The higher the drug selectivity the lower the risk of undesirable action. Affinity is a measure of how avidly the drug binds to its receptor. The long acting β2-agonists (LABA) have been characterized by nearly 50-fold higher affinity than the short acting drugs (salbutamol, fenoterol). It mainly depends on their biological structure. Efficacy is key parameter and refers to the ability of a drug to activate its receptor, regardless of drug concentration. Complete receptor activation is characteristic for a full agonist, while partial activation - to a partial agonist. In the beta2 agonists group fenoterol and formoterol are full agonists, salmeterol and salbutamol - partial agonists.

Very important for receptor’s reaction is desensitization – one of major process of receptor autoregulation. Desensitization can occur according to at least three mechanisms: full – reversible receptor uncoupling or shedding, receptor internalization or/and a non-reversible process of “down- regulation”. Full β-agonists provide more rapid desensitization than partial agonists. A full knowledge of both receptor and agonist characteristics allows, in every drug group, to chose optimal substances with highest possible level of desired (therapeutic) effect and minimal side effects.

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