Efficacy. II. Estimation of a newly defined efficacy related parameter.
A new method for estimation of agonist-affinity (KA) and relative efficacy was introduced. This method afforded a procedure by which relative efficacy may be estimated while the actual KA values of agonist-receptor complexes are unknown. The relative efficacy may be estimated by employing a newly defined drug parameter, namely the eES value. The eES value is related to drug efficacy and is defined in such a manner that an isolated eES is a meaningful quantity which may indicate whether or not spare receptors are present in an agonist-effector system. The estimation of eES was based on the fact that fixed agonist-competitive antagonist combinations mimic partial agonists and mediate submaximal concentration-effect curves. However, for the practical estimation of eES one may employ data acquired from agonistic concentration-effect curves determined in the absence and presence of increasing concentrations of a competitive antagonist. This procedure was illustrated by utilizing theoretical concentration-effect curves and applied practically by estimating eES and KA values acquired from sets of carbachol and salbutamol curves. The sets of carbachol and salbutamol concentration-effect curves were determined in the absence and presence of their respective competitive antagonists, namely tripitramine and pindolol.
Venter
D P
DP
Department of Pharmacology, Potchefstroom University for Christian Higher Education, South Africa. fkldpv@puknet.puk.ac.za
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D004336:Drug Antagonism; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D018721:Muscarinic Agonists / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D010600:Pharmacology / Q000379:methods*; D010869:Pindolol / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D043587:Receptor, Muscarinic M3; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018721:Muscarinic Agonists; D043587:Receptor, Muscarinic M3; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D002217:Carbachol; D010869:Pindolol; D000420:Albuterol