P-sympatholytics

Nevertheless, this method was successfully applied by Gulyaeva et al. for the log P and log D determination of 15 P-sympatholytic drugs [56]. Another study by Welerowicz and Buszewski compared the HpophiHcity values of P-blockers obtained with a column made of a monoHthic-silica Cjg with a conventional porous silica particles Cjg as reference material [27]. A modified method was used for evaluating logP with two main differences (i) logfeg was considered rather than retention times, and (ii) benzene and butyl-benzene were used as calibration compounds. 

P-Sympatholytics are antagonists of norepiphephrine and epinephrine at p-adrenoceptors they lack affinity for a-receptors. 

The basic structure shared by most 3-sympatholytics is the side chain of 3-sympathomimetics (cf isoproterenol with the p-blockers propranolol, pindolol, atenolol). As a rule, this basic structure is linked to an aromatic nucleus by a methylene and oxygen bridge. The side chain C-atom bearing the hydroxyl group forms the chiral center. With some exceptions (e.g., timolol, penbuto-lol), all p-sympatholytics are brought as racemates into the market (p. 62). 

Some p-sympatholytics possess higher affinity for cardiac Pi-receptors than for P2-receptors and thus display cardioselectivity (e.g., metoprolol, ace-butolol, bisoprolol). None of these blockers is sufficiently selective to per-Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

B. Avalanche-like increase in commercially available P-sympatholytics... 

The chemical structure of p-blockers also determines their pharmacokinetic properties. Except for hydrophilic representatives (atenolol), p-sympatholytics are completely absorbed from the intestines and subsequently undergo presystemic elimination to a major extent (A). 

These stereoisomers provide an example of different but complementary pharmacological of stereoisomers contributing to overall therapeutic utility, i. i -labetalol is a selective P-sympatholytic whiole the 5,i -isomer is an tti-adrenolytic eutomer. 

Thesis Lipid-mobilizing effects of sympathomimetics are in general related to the degree of their p-tropism the affinities of various catecholamines show, however, notably weaker differences than is the case in various oxedrines. In contradistinction to a-sympathol) cs, the P-sympatholytic agents antagonize the adrenergic lipid mobilization competitively and highly specifically. 

It is true, however, that lipid mobilization can be evoked by substances possessing no P-sympathomimetic action and can be inhibited by substances possessing no P-sympatholytic effect. For a solution of the question of whether the lipid mobilization affected by sympatho-tropic substances is to be regarded essentially as a specifically adrenergic reaction, the action of the following compounds and groups would seem to be of importance. 

As noted, serotonin synthesis can be inhibited by p-chlorophenylalanine and p-chloroamphetamine. However, these agents are too toxic for general use. Storage of serotonin can be inhibited by the use of reserpine, but the sympatholytic effects of this drug (see Chapter 11) and the high levels of circulating serotonin that result from release prevent its use in carcinoid. Therefore, receptor blockade is the major therapeutic approach to conditions of serotonin excess. 

Central-acting sympatholytics (e.g., clonidine and methyldopa) Peripheral-acting sympatholytics (e.g., guanadrel) p-blockers Thiazides Anticholinergics Antidepressants... 

From the influence of the autonomic nervous system it follows that all sympatholytic or sympathomimetic and parasympatholytic or parasympathomimetic drugs can produce corresponding effects on cardiac performance. These possibilities are exploited therapeutically for instance, p-blockers for suppressing excessive sympathetic drive (p. 96) ipratropium for treating sinus bradycardia (p. 108). An unwanted activation of the sympathetic system can result from anxiety, pain, and other emotional stress. In these cases, the heart can be protected from harmful stimulation by psychopharmaceuticals such as benzodiazepines (diazepam and others important in myocardial infarction). 

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p.110) and Hq-antihistaminics (p.118) of the diphenylmethane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all para-sympatholytics or antihistaminics. The ef -cacy of the drugs mentioned depends on the actual situation of the individual (gastric filling, ethanol consumption), environmental conditions (e.g., the behavior of fellow trav-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

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