The history and derivation of the Schild equation is reviewed as well as the conditions under which the intercept of a Schild regression (the pA2, an empirical quantity) can be considered to be an estimate of the equilibrium dissociation constant of the antagonist for the receptor (KB). This parameter is of value in the classification of receptors. To be considered competitive (and, therefore, to be described in molecular terms by a KB), an antagonist must produce parallel displacement of agonist concentration-response curves with no alteration in the maximal response and thereby yield unambiguous dose ratios of agonist which are independent of agonist concentration. These dose ratios (dr) then can be utilized in the Schild equation (log (dr = 1) = n . log [B] - log KB, where [B] is the molar concentration of antagonist) in the form of a regression of log (dr - 1) on log [B]. If the regression is linear and has a slope of unity, the blockade is consistent with simple competitive antagonism and the intercept can be considered an estimate of the KB. Experimentally, the slope is a parameter critical to the assessment of competitivity. While a slope significantly different from unity may indicate that an antagonist is not competiti...Continue Reading
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A model for the interaction of competitive antagonists with two receptor-subtypes characterized by a Schild-plot with apparent slope unity. Agonist-dependent enantiomeric affinity ratios for bupranolol in tracheae but not in right atria of guinea pigs
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Muscarinic M1- and M2-receptors mediating opposite effects on neuromuscular transmission in rabbit vas deferens
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Pharmacological characterization using selected antagonists of the leukotriene receptors mediating contraction of guinea-pig trachea
Modification by desipramine of the effects of alpha-adrenoceptor antagonists on the contractile responses of the trisected rat vas deferens
Action of different agonists and antagonists of the cholinergic system on the rat lower esophageal sphincter
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Antagonism of kinin-induced contraction of isolated rat uterus by the crude hydroalcoholic extract from Mandevilla illustris
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Failure of AH11110A to functionally discriminate between alpha(1)-adrenoceptor subtypes A, B and D or between alpha(1)- and alpha(2)-adrenoceptors
Heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein
Hippocampal hyperexcitability induced by GABA withdrawal is due to down-regulation of GABA(A) receptors
Combined histamine H1/H2 receptor antagonists: part I. Pharmacological hybrids with pheniramine- and roxatidine-like substructures
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Investigation of alpha1-adrenoceptor subtypes mediating vasoconstriction in rabbit cutaneous resistance arteries
Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery
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Subclassification of beta-adrenoceptors responsible for steroidogenesis in primary cultures of bovine adrenocortical zona fasciculata/reticularis cells
Alpha-adrenoceptor subtypes in dog saphenous vein that mediate contraction and inositol phosphate production
Estimation of competitive antagonist affinity from functional inhibition curves using the Gaddum, Schild and Cheng-Prusoff equations
Analysis of the effects of alpha 1-adrenoceptor antagonists on noradrenaline-mediated contraction of rat small mesenteric artery
Adenosine antagonism and related effects of theophylline derivatives in guinea pig ileum longitudinal muscle
Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys: antagonism and apparent pA2 analyses
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Purinergic P2X3 heteroreceptors enhance parasympathetic motor drive in isolated porcine detrusor, a reliable model for development of P2X selective blockers for detrusor hyperactivity
Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins
Protein engineering and preclinical development of a GM-CSF receptor antibody for the treatment of rheumatoid arthritis
Pharmacological characterization of a substance P antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P
Tryptamine-induced vasoconstrictor responses in rat caudal arteries are mediated predominantly via 5-hydroxytryptamine receptors
The competitive antagonistic effect of compounds from Mandevilla velutina on kinin-induced contractions of rat uterus and guinea-pig ileum in vitro
The relative contribution of affinity and efficacy to agonist activity: organ selectivity of noradrenaline and oxymetazoline with reference to the classification of drug receptors
Activity of nonpeptide tachykinin antagonists on neurokinin a induced contractions in dog urinary bladder
Involvement of β3-adrenoceptors in the inhibitory control of cholinergic activity in human bladder: Direct evidence by [(3)H]-acetylcholine release experiments in the isolated detrusor
Pharmacological and signalling properties of a D2-like dopamine receptor (Dop3) in Tribolium castaneum
Vasoconstrictor effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F(2alpha) on human umbilical vein
Synthesis and pharmacology of combined histamine H1-/H2-receptor antagonists containing diphenhydramine and cyproheptadine derivatives
AH23848: a thromboxane receptor-blocking drug that can clarify the pathophysiologic role of thromboxane A2
Theoretical and functional studies on alpha 1-and alpha 2-adrenoreceptors: an examination using the Schild plot
Interactions of dimethoxy-substituted tolazoline derivatives with alpha 1- and alpha 2-adrenoreceptors in vitro
The actions of histamine on the separated layers of the guinea-pig uterus: the influence of ovarian steroids
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Structure-activity relationship on (+/-)-nantenine derivatives in antiserotonergic activities in rat aorta
Down-regulation of melanocortin receptor signaling mediated by the amino terminus of Agouti protein in Xenopus melanophores.
Protein prenylation contributes to the effects of LPS on EFS-induced responses in human isolated bronchi
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