Functional antagonism

Sympatholytics Drugs that inhibit or antagonize function within the sympathetic nervous system. 

Nagpal, S., Athanikar, J., and Chandraratna, R.A., Separation of transactivation and API antagonism functions of retinoic acid receptor alpha, J. Biol. Chem., 270, 923, 1995. 

Reserpine Antagonism functional biochem. functional none... 

The mechanism by which the methylxanthines produce CNS stimulation is not clearly estabUshed. These agents may function, ia part, to limit chloride channel activation ia a manner similar to that of pentylenetetra2ol (7) or hicuculline (8). Another possibiUty is a specific antagonism of the inhibitory neurotransmitter adenosiae [58-61-7] (19) (19). 

It has by now been reasonably well established that an ethanolamine function appropriately linked to an aromatic ring is a prerequisite for beta adrenergic activity and/or antagonism. Examples have been met above where those two moieties are attached directly as well as examples where the funetions are separated by an oxymethylene fragment. It has reeently been found that beta blocking activity is retained even when a earbonyl is inserted between the extra oxymethylene... 

FIGURE 6.6 Schilcl regression for pirenzepine antagonism of rat tracheal responses to carbachol. (a) Dose-response curves to carbachol in the absence (open circles, n = 20) and presence of pirenzepine 300 nM (filled squares, n = 4), 1 jjM (open diamonds, n=4), 3j.lM (filled inverted triangles, n = 6), and 10j.iM (open triangles, n = 6). Data fit to functions of constant maximum and slope, (b) Schild plot for antagonism shown in panel A. Ordinates Log (DR-1) values. Abscissae logarithms of molar concentrations of pirenzepine. Dotted line shows best line linear plot. Slope = 1.1 + 0.2 95% confidence limits = 0.9 to 1.15. Solid line is the best fit line with linear slope. pKB = 6.92. Redrawn from [5],... 

Schild analysis, like all pharmacological tools, necessarily is predicated on the idea that the drugs involved have one and only one pharmacological activity. This often may not be the case and selectivity is only a function of concentration. If the concentrations used in the assay are below those that have secondary effects, then the tool will furnish the parameter of interest with no obfuscation. However, if a secondary effects are operative in the concentration range required to measure antagonism then the resulting parameter may be tainted by this secondary activity. 

Equation 7.6 defines the allosteric noncompetitive antagonism of receptor function and predicts insurmountable effects on agonist maximal response (i.e., as [A] oo) the expression for maximal response is... 

Sole effects on affinity (with no change in receptor function) result in surmountable antagonism. 

Allosteric modulators that block receptor function produce insurmountable antagonism. In addition, modulators that block function also can alter (increase or decrease) affinity. 

Functional antagonism, reduction in the responsiveness to a given agonist by activation of cellular mechanisms that produce a counterstimulus to the cell. 

Ag, convention for the equilibrium dissociation constant of an antagonist-receptor complex usually determined in a functional assay denoting antagonism of a physiological response, although it can be associated with an antagonist when it is used in other types of experiment. It has units of M and is the concentration that occupies half the receptor population at equilibrium. It also can be thought of as the reciprocal of affinity. 

One-way analysis of variance, 229-230, 230f—231f Operational model derivation of, 54-55 description of, 45—47, 46f function for variable slope, 55 for inverse agonists, 221 of agonism, 47f orthosteric antagonism, 222 partial agonists with, 124, 220-221 Opium, 147 Orphan receptors, 180 Orthosteric antagonism... 

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