β-ADRENOCEPTOR AGONISTS

β-ADRENOCEPTOR AGONISTS (also known as β-adrenergic receptor agonists or β-receptor stimulants) are a class of drugs that act through stimulating β-adrenoceptors, and thus induce some actions of the sympathetic nervous system by mimicking the action of adrenaline and noradrenaline — catecholamine mediators acting predominantly as hormone or neurotransmitter, respectively. The actions of α-adrenoceptor and β-adrenoceptor activation together account for nearly all the very widespread actions of the sympathetic division of the autonomic nervous system, both in normal physiology and in stress. Among other actions, β-adrenoceptors have cardiac stimulant actions, they dilate certain blood vessels, suppress motility within the gastrointestinal tract, bladder and uterus, and stimulate certain aspects of metabolism causing an increase in glucose and free fatty acids in the blood. These actions, in concert with α-adrenoceptors help prepare the body for emergency action.

These actions are commonly mimicked for clinical purposes, but effects tend to be widespread. However, it is possible to gain some selectivity of drug action, with consequent minimization of side-effects, by using receptor-subtype-selective β-adrenoceptor agonists. Thus, β1 adrenoceptor-selective agonists are more active on the heart, and β2-adrenoceptor-selective agonists are more active at most other sites in the body, including the airways. It is necessary to use β2-adrenoceptor-selective stimulant drugs to achieve bronchodilation in the widespread common treatment of acute asthma (see antiasthmatics; BRONCHODILATORS); otherwise there may be significant — and potentially dangerous — stimulation of the heart. Another use of β2-adrenoceptor agonists is to relax the uterus in premature labour. Conversely, β1-adrenoceptor agonists (e.g. dobutamine, rimiterol, xamoterol) or non-selective β-adrenoceptor agonists (e.g. noradrenaline) are sometimes used to stimulate the failing heart. Examples of β2-adrenoceptor agonist drugs used clinically are bambuterol, fenoterol, salbutamol. salmeterol and terbutaline. Recently, a third type of receptor called ‘atypical β’, or β3-adrenoceptors, has been cloned and also shown to be involved in certain functional responses, including lipid metabolism; but many agonist ligands active at this site are also fairly active at the other two sites. However, some such ligands may be used to treat diabetes, for instance, CL 316243. Carazolol is used as an analytical tool since it has a high affinity for the β3-adrenoceptor where it acts as an agonist, but it is also an antagonist at the β1– and β2-sites.

All three receptors are of the seven-transmembrane superfamily and are positively coupled to adenylyl cyclase. In addition to β-adrenoceptor agonists, indirect SYMPATHOMIMETICS may cause the eventual activation of β-adrenoceptors (or α-adrenoceptors), depending on tissue factors, by causing release of noradrenaline (e.g. ephedrine, pseudoephedrine) or preventing noradrenaline reuptake (e.g. cocaine).