Beta adrenoceptor agonists/antagonists

Ruffolo, R.R. (1991) Chirality in alpha- and beta-adrenoceptor agonists and antagonists. Tetrahedron 47 4953-4980. 

Alpha adrenoceptor agonists Beta adrenoceptor agonists Beta adrenoceptor antagonists ACE inhibitors... 

Because iCg values for competitive antagonists represent tme dissociation constants, these make possible quantitative interpretations of SARs. Significant use also has been made of iCg values in the quantitative comparison of receptors to determine whether receptors that respond to the same agonists are identical or whether responses produced by different agonists are initiated at the same receptors (44,46). Thus, beta-adrenoceptors in human and guinea pig preparations can be direcdy compared and selective and antagonists quantitated (Table 3). 

It is to be expected that a drug with an agonist action at a particular receptor type will interact with antagonists at that receptor. For example, the bron-chodilator action of a selective beta-2-adrenoceptor agonist such as salbutamol will be antagonised by non-selective beta-adrenoceptor antagonsists. 

Beta-adrenoceptor antagonists, particularly propranolol, have been shown to be effective for anxiety symptoms particularly in situational anxiety and GAD. Buspirone, an azaspirodecanedione, is an agonist at 5-HTlA receptors and seems to have anxiolytic effects, though it is less potent than the BDZs and the effects take up to three weeks to become evident. There is high first pass metabolism and a considerable proportion of the effect is due to a metabolite (1-PP). The principal adverse effects of buspirone are nausea, gastrointestinal upset and headache. Antidepressant drugs, both the older tricyclic antidepressants and the newer drugs, have been demonstrated to have anxiolytic effects in mixed anxiety-depressive patients, GAD and panic disorder. 

Q10 Beta-adrenoceptor antagonists are contraindicated in patients with asthma or respiratory obstructive diseases, bradycardia, heart block or heart failure. Adrenergic agonists are contraindicated in patients with closed-angle glaucoma and should be used cautiously in patients with hypertension or heart disease. Parasympathomimetics cause poor night vision and dimming of vision, because of development of miosis, headache and brow ache. Carbonic anhydrase inhibitors have a weak diuretic action and can induce depression, drowsiness, paraesthesia, electrolyte disturbance such as hypokalaemia, acidosis and lack of appetite. 

Although atenolol, a hydrophihc cardioselective beta-adrenoceptor antagonist with no partial agonist activity, is generally regarded as one of the safest beta-blockers, severe adverse effects are occasionally reported. These include profound hypotension after a single oral dose (1), organic brain syndrome (2), cholestasis (3), and cutaneous vascuhtis (4). 

Many beta-adrenoceptor antagonists (beta-blockers) have been developed, and their adverse effects have been comprehensively reviewed (1). The spectmm of adverse effects is broadly similar for aU beta-blockers, despite differences in their pharmacological properties, notably cardioselectiv-ity, partial agonist activity, membrane-stabilizing activity, and lipid solnbUity (see Table 1). The inflnence of these properties is mentioned in the general discnssion when appropriate and is snmmarized at the end of the section. Individnal differences in toxicity are largely nnimportant bnt win be mentioned briefly. 

Although there are now many different beta-adrenoceptor antagonists, and the number is still increasing, there are only a few important characteristics that distinguish them in terms of their physicochemical and pharmacological properties Upid solubility, cardioselectivity, partial agonist activity, and membrane-stabilizing activity. The characteristics of the currently available compounds are shown in Table 1. 

Beta-blockade can result in sinus bradycardia, because blockade of sympathetic tone allows unopposed parasympathetic activity. Drugs with partial agonist activity may prevent bradycardia (52). However, heart rates under 60/ minute often worry the physician more than the patient in a retrospective study of nearly 7000 patients taking beta-adrenoceptor antagonists, apart from dizziness in patients with heart rates under 40/minute (0.4% of the total group), slow heart rates were well tolerated (53). 

Pindolol is a beta-adrenoceptor antagonist with beta2-adrenoceptor agonist action and some membrane-stabilizing activity (1). 

Practolol is a highly cardioselective beta-adrenoceptor antagonist with partial agonist activity. 

Goldberg MR, Sciberras D, De Smet M, Lowry R, Tomasko L, Lee Y, Olah TV, Zhao J, Vyas KP, Halpin R, Kari PH, James I. Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HTib id agonist differential effects of propranolol, nadolol and metoprolol. Br J Qin Pharmacol 2001 52(l) 69-76. 

Xamoterol is a beta-adrenoceptor antagonist/partial agonist that was developed for use in mild cases of cardiac failure and to treat atrial fibrillation (1). In more severe cases, however, it can actually worsen heart failure and increase mortality (2), because when sympathetic nervous system activity is high its beta-adrenoceptor antagonist properties predominate. It has therefore been withdrawn from the market (SEDA-18,159). 

Indenolol is a new antihypertensive agent with beta,-adrenoceptor antagonist and beta2-adrenoceptor agonist properties. 

Two commonly used drugs in human medicine, terbutaline and propranolol, have been tested concerning their effect on erythrocyte metabolism. Terbutaline is a beta-2-adrenoceptor agonist and propranolol is a beta-l-beta-2-adrenoceptor antagonist. Both drugs are taken up into the erythrocytes. 

---