Antagonists defined

Barker, E. L., Perlman, M. A., Adkins, E. M Houlihan, W. J., Pristupa, Z. B Niznik, H. B and Blakely, R. D. (1998) High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol. J. Biol. Chem. 273, 19459-19468. 

The actions of histamine are mediated through at least three distinct receptors defined pharmacologically by the actions of the respective agonists and antagonists. Reviews have been pubHshed (16,17). 

Phentolamine (87), WB 4101 (88), and the site directed alkylatiag agent, chloroethylclonidine (CEC) (89) have been traditionally used to define a -receptors. Table 6 Hsts the various catecholamines and adrenoreceptor agonists and antagonists. 

The term intrinsic activity (ia) was defined as a measure of the abiUty of the dmg—receptor complex to generate response. When ia = 1, a full agonist is defined when ia = 0, an antagonist is defined. Thus, values 0 < ia < 1 define partial agonists as follows, where R is the response to dmg and R is the maximum response achieved. 

It can be seen that the equality defined in Equation 4.32 is true only when ICSo = KB (i.e., the concentration of a non-competitive antagonist that reduces the binding of a tracer ligand by 50% is equal to the equilibrium dissociation constant of the antagonist-receptor complex). 

The concentration of allosteric antagonist [B] that reduces a signal from a bound amount [A ] of radioligand by 50% is defined as the IC50 ... 

An agonist and antagonist to define the response on the target are available. 

The concentration of antagonist producing a 50% diminution of the agonist response to concentration [A] is defined as the ICSo for the antagonist. Therefore ... 

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). 

Adenosine Receptors. Table 2 Affinity of commonly used adenosine receptor agonists and antagonists for defining pharmacologically adenosine receptor subtypes... 

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