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). 

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. 

Omission of the side chain hydroxyl group from molecules based on epinephrine or ephedrine does not abolish the sympathomimetic activity of the resulting compounds. Many of these agents exert a considerable stimulant action on the central nervous system. As such, drugs in this class have been widely used—and... 

Unless contraindicated ACE, angiotensin-converting enzyme, ISA, intrinsic FIGURE 42-1. Algorithm for the sympathomimetic activity... 

FIGURE 2-4. Flowchart listing various P-blocking agents separated by P-receptor activity and intrinsic sympathomimetic activity. 

International Verapamil-Trandolapril Study Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study intrinsic sympathomimetic activity intravenous... 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Modifying the way in which the aromatic system was linked to the ethanolamine moiety led to the oxypropranolamines as typified by propranolol. It is 10-20 times more potent than pronethalol and shows no intrinsic sympathomimetic activity. 

Thus the "ideal" anti-hypertensive 3-blocking agent should be a moderately long acting cardioselective agent showing little or no intrinsic sympathomimetic activity. 

Figure 27. Comparison of the relationship between antihypertensive and sympathomimetic activity and sedation and inhibition of gastric secretion of clonidine and two derivatives (St 600 and St 608). The antihypertensive activity was tested in genetic hypertensive rats. The sympathomimetic activity was measured as blood pressure increase in spinal rats. The sleep effect in chicks was tested according to the method in Reference 50, and the gastric secretion in rats was measured according to the method in Reference 57.

The tetrahydrobenzazepine (LXIX) related to debrisoquine (LXVII) is reported to be a potent adrenergic neurone blocking agent (three-fifths as potent as guanethidine in anaesthetized cats) [280]. Marked sympathomimetic activity is not associated with (LXIX) and in this respect it is similar to the hexahydrobenzazo-... 

Unlike guanethidine, t-octylguanidine shows little sympathomimetic activity. A direct vasodilatation has been demonstrated, but it is doubtful whether this plays a very important role in the action of this drug. The possibility of a central... 

Absence of one or both aromatic hydroxyl groups is associated with an increase in indirect sympathomimetic activity, denoting the ability of a substance to release norepinephrine from its neuronal stores without exerting an agonist action at the adrenoceptor (p. 88). 

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. 

Sympathomimetic activity is maximal when there are two carbon atoms between the aromatic ring and the amino group. 

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