Drug antagonism receptor

Competition for receptors, hence receptor antagonism, is governed by the law of mass action that is, the interaction between drug and receptor depends on the concentration of drug in the vicinity of the receptor and the number of receptors present. Because agonist and antagonist have an affinity for the same receptors, the two substances compete for binding to the receptors. 

On receptor basis, drug antagonism will be of two types competitive and noncompetitive antagonism. 

Drugs that preferentially block the [ receptors have been developed to eliminate the unwanted bronchoconstrictor effect (p2) of propranolol seen among asthmatic patients. Cardioselective p-blockers, such as acebutolol [a se BYOO toe lole], atenolol [a TEN oh lole], and metoprolol [me TOE proe lole], antagonize receptors at closes 50 to 100 times less than those required to block p2 receptors. This cardioselectivity is thus most pronounced at low doses and is lost at high drug doses. [Note Acebutolol has some intrinsic agonist activity.]... 

It appears to the writer that the most important fact shown by a study of drug antagonisms is that it is impossible to explain the remarkable effects observed except by assuming that drugs unite with receptors of a highly specific pattern. No other explanation will, however, explain a tithe of the facts observed. 

Lepre, C.A., Garcia-Guzman, M., and Moore, J.M. (2010) Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure, 18, 1083-1093. 

Some alicyclic 1,2-diamine derivatives have recently been shown to have interesting CNS properties. For example, eclanamine (34) is an antidepressant with a rapid onset of action. The reasons for its potency are not as yet clear but pharmacologists note that the drug desensitizes adrenergic alpha-2 receptors and antagonizes the actions of clonidine. The synthesis of eclanamine starts with attack of cyclopentene oxide (30) by dimethylamine (to give 31). This product is converted to the mesylate by reaction with sodium hydride followed by mesyl chloride. Attack of... 

Some of the side effects due to beta blockers such as the slowing of heart rate can be counteracted by administration of drugs which antagonize the alpha adrenergic receptors. The... 

Uncompetitive antagonism, form of inhibition (originally defined for enzyme kinetics) in which both the maximal asymptotic value of the response and the equilibrium dissociation constant of the activator (i.e., agonist) are reduced by the antagonist. This differs from noncompetitive antagonism where the affinity of the receptor for the activating drug is not altered. Uncompetitive effects can occur due to allosteric modulation of receptor activity by an allosteric modulator (see Chapter 6.4). 

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