Pharmacological actions

Biologica.1 Activities a.ndAna.logues, The many pharmacological actions of neurotensin include hypotension, increased vascular permeabihty, hyperglycemia, increased intestinal motility, and inhibition of gastric acid secretion (120). In the brain, it produces analgesia at remarkably low doses (121). 

Dmg receptors represent another type of receptor family. The central nervous system (CNS) effects of the anxiolytic, diazepam, and the psychotropic actions of the caimabiaoids and phencycUdine have resulted ia the identification of specific receptors for these molecules. This has resulted ia the search for an endogenous ligand for these receptors. Thus, ia these situations, the pharmacological action has preceded the discovery of the receptor which, ia turn, has provided clues ia several iastances to the endogenous ligand. 

The precise mechanism of nitrate action is not cleady understood and may be a combination of many factors. The basic pharmacologic action of nitrates is a relaxation of most vascular smooth muscle, eg, vascular, bronchial, gastrointestinal, uretal, uterine, etc. Vascular smooth muscle relaxation is a... 

Choline dihydrogen citrate (CH2)3N(CH2CH20H)C H202, is prepared by methods similar to those for preparing choline chloride. It has the same pharmacological action as the chloride, but contains a lower proportion of choline. It is not as dehquescent as the chloride, and absorbs moisture from the atmosphere only at relative humidities greater than 56% at 25.5°C. It is mote palatable than the chloride. 

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

Neither tropine nor 4-tropine is mydriatic, though the former is stated to produce mydriasis in cats when injected in large doses. The pharmacological properties of these two bases have been compared by Hazard, who points out that these cis-trans isomerides show qualitative differences in pharmacological action, whereas among optical isomerides there are usually only quantitative differences in activity. It has been stated that rabbits are immune from poisoning by belladonna and, in that connection,... 

According to Nyman the pharmacological action of hyoscine is considerably modified in the quaternary compounds of the alkaloid, e.g., the inhibiting action on salivary secretion is greatly increased in the methonitrate, as is also the spasmolytic activity, but the mydriatic action is unchanged and the central sedative activity disappears. 

These results indicate that in these new ester mydriatics, the structural factors, which influence the development of this type of pharmacological action are similar to those made evident by the chemical investigations of Jowett and Pyman and the pharmacological work of Marshall, Dale, Laidlaw and Cushny on the tropeines. The nature of the basic component is obviously important since mydriasis is produced by simple bases such as ephedrine. As regards the nature of the esterifying acid, Jowett and Pyman drew the following conclusions — ... 

To these may be added Blicke and Kaplan s conclusion, that the nature of the basic nucleus and the relative positions of the phenyl and hydroxyl groups in the esterifying acid are of prime importance. These conclusions do not provide a full explanation of the results of these investigations. It seems clear that chemical structure alone provides an insufficient basis and that molecular size and shape and other physical properties of the substance play a considerable part in determining the pharmacological action. 

Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

The pharmacological action of bases from Cereus coryne Solm, Pachycereus marginatus, Trichocereus terscheki, Britton and Rose, and T. candicans B. and R., has also been recorded. T. terscheki is stated to contain trichocereine (A-dimethylmezcaline) and 3 4-dihydroxyphenyl-ethyltrimethylammonium hydroxide. The latter is probably also present in Cereus coryne. T. candicans is stated to contain hordenine (anhaline) and p-hydroxyphenylethyltrimethylammonium hydroxide (candicine). 

These early observations on the correlation of structure and pharmacological action in the morphine group have been greatly extended as a result of chemical, pharmacological and clinical work done under the auspices of the American National Committee on Drug Addiction. In addition to numerous papers, contributed by experts serving this Committee, to chemical and pharmacological journals, two important reports have been published —... 

These general results have entailed much detailed chemical and pharmacological work on the influence of structural changes on particular items in the pharmacological action of morphine, e.g., its effect on respiration. ... 

In 1939 Eisleb and Schaumann described the pharmacological action of ethyl 4-phenyl-l-methylpiperidine-4-carboxylate,... 

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