Partial agonists intrinsic sympathomimetic activity

Some P-adrenoceptor blockers have intrinsic sympathomimetic activity (ISA) or partial agonist activity (PAA). They activate P-adrenoceptors before blocking them. Theoretically, patients taking P-adrenoceptor blockers with ISA should not have cold extremities because the dmg produces minimal decreases in peripheral blood flow (smaller increases in resistance). In addition, these agents should produce minimal depression of heart rate and cardiac output, either at rest or during exercise (36). 

The side chain and substituents on the amino group critically affect affinity for P-receptors, whereas the aromatic nucleus determines whether the compound possess intrinsic sympathomimetic activity (ISA), that is, acts as a partial agonist (p. 60) or partial antagonist. In the presence of a partial agonist (e.g., pindolol), the ability of a full agonist (e.g., isoprenaline) to elicit a maximal effect would be attenuated, because binding of the full agonist is impeded. names. 

The similarity in structure to (3-agonists is most certainly responsible for the finding that some (3-blockers activate (3-receptors that is, they have some intrinsic sympathomimetic activity. The intrinsic activity of these compounds is generally modest in comparison with an agonist, such as isoproterenol, and they are generally referred to as partial agonists (see Chapter 2). 

Pindolol, acebutolol, and penbutolol are partial agonists, ie, 3 blockers with some intrinsic sympathomimetic activity. They lower blood pressure by decreasing vascular resistance and appear to depress cardiac output or heart rate less than other 3 blockers, perhaps because of significantly greater agonist than antagonist effects at 32 receptors. This may be particularly beneficial for patients with... 

Intrinsic sympathomimetic activity (ISA)—less bradycardia and minimal change in plasma lipids. These are partial agonists. 

The ability to show at least partial p-receptor blockade in a way constituted the missing piece of evidence needed for wide acceptability of the a P receptor concept as reality. Further work ultimately showed the compound was not a pure blocker since it had some agonist activity as well. It is referred to today as partial intrinsic sympathomimetic activity (ISA). This property eliminated the compound s clinical potential. However, as will be seen, it did ultimately lead to a new group of therapeutically important P-blockers. 

PHARMACOLOGICAL EFFECTS The fi blockers vary in their lipid solubility, selectivity for the /Ij adrenergic receptor subtype, presence of partial agonist or intrinsic sympathomimetic activity, and membrane-stabilizing properties. While all of the P receptor antagonists are effective... 

Intrinsic sympathomimetic activity (ISA) Partial agonist action by adrenoceptor blockers typical of several beta blockers, eg, pindolol, acebutolol... 

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