Intrinsic sympathomimetic activity ISA

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). 

P-Adrenoceptor blockers for the treatment of hypertension include (/) the cardioselective P -adrenoceptor blockers without intrinsic sympathomimetic activity (ISA), ie, atenolol (Table 3), bisoprolol (Table 3), and metoprolol (Table 1) (2) the cardioselective with ISA, ie, acebutolol (Table 1) (J) the noncardioselective without ISA, ie, propranolol (Table 1) and timolol [26839-75-8] C23H24N4O2S and (4) the noncardioselective with ISA, ie, oxprenolol [6452-71-7] C 3H23N03, and pindolol. 

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. 

Due to the numerous indications for these type of drugs a large number of compounds have been introduced into therapy. Differences between these drugs concern their affinity profile towards the Pi-and j82-adrenoceptors, the lipophilicity and the ability to partially activate the receptor (intrinsic sympathomimetic activity, ISA). One isomer of the racemic mixture of labetalol and carvedilol are a-blocker as well. Although this might be therapeutically useful in the treatment of conditions like hypertension and heart failure, there is no real evidence for a contribution of this property to the overall beneficial effect of these compounds. 

Beta-adrenergic blocking agents, SELECTIVE, intrinsic SYMPATHOMIMETIC ACTIVITY (ISA)... 

Beta-adrenergic blocking agents, selective, intrinsic sympathomimetic activity (ISA) acebutolol hydrochloride... 

Timolol is a noncardioselective P-blocker without intrinsic sympathomimetic activity (ISA). Antagonism of the P2-adrenoceptor at the ciliary body is primarily responsible for the ocular hypotensive efficacy of timolol. 

Several mechanisms of action have been proposed for /3-adrenoceptor blockers (/S-blockers), but none of them alone has been shown to be associated consistently with a reduction in arterial BP. /3-Blockers have negative chronotropic and inotropic cardiac effects that reduce cardiac output, which explains some of the antihypertensive effect. However, cardiac output falls equally in patients treated with /3-blockers regardless of BP lowering. Additionally, /3-blockers with intrinsic sympathomimetic activity (ISA) do not reduce cardiac output, yet they lower BP and decrease peripheral resistance. 

There is no evidence to suggest that there is a specific therapeutic advantage to one -blocker over another. Selective and nonselective /3-blockers appear equally effective in DHF. /3-Blockers with intrinsic sympathomimetic activity (ISA) may be less effective because they slow the heart rate less. In general, it is not necessary to start the drug at an extremely low dose and titrate the 8-blocker in a slow, progressive fashion in DHF, as it is in SHF. Since the population is older, it is prudent to start with a moderate dose of 8-blockers, snch as metoprolol 25 mg twice daily or atenolol 25 mg/day and titrate to a higher dose with a treatment target of a heart rate of approximately 60 beats per minnte. 

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

Prototype drug, but many other beta blockers are used in HTN (see ANS section, Chapter 3, for specifics on cardloselective drugs and those with intrinsic sympathomimetic activity [ISA]). All appear to be equally effective with respect to HTN. 

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. 

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

Practolol was found to be less potent than propranolol. It also exhibited intrinsic sympathomimetic activity (ISA) to a certain extent. It is pertinent to state here that one particular property not earlier observed with the P-blockers the ability predominantly to inhibit isoproterenol (IPR)-induced tachycardia, while exhibiting a minimal or no effect on the IPR-depressor i.e., hypotensive) response. In other words, practolol displayed cardioselectivity. Hence, for the first ever instance it was revealed and evidenced that the inhibition of P-adrenergic response may be confined significantly to certain sites. 

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