Affinity, drug-receptor

Rational design, 148-149, 152 Real-time assays, 83, 88 Receptor(s). See also Drug receptors affinity for, 6, 63 allosteric model of, 143 Clark s work, 3 classical model of, 44-45 concept of, 2-4 conformations, 13-14, 13 Of conservation equation for, 76 constitutive activity of, 49-51 coupling of, 27 definition of, 2 desensitization of, 34 efficacy for, 6... 

A basic premise in receptor pharmacology is that all drugs have affinity for receptors (the chemical property that unites the dmg with the receptor), and some drugs have efficacy, the chemical property that causes the receptor to change its behavior toward its host cell. Drugs that have efficacy can produce concentration-dependent responses in physiological systems, characterized by a concentration-response curve (also often referred to as a dose-response cuive). 

Drug-Receptor Interaction. Figure 2 Relationships between affinity and efficacy with different agonist response patterns, (a) For partial agonists, differences in maximal responses between agonists relate to differences in efficacy. Differences in the location parameter of the concentration-response curve (potency) indicate differences in affinity, (b) For full agonists, differences in potency indicate differences in either affinity, efficacy or both. 

The dissociation constant for the drug-receptor complex. It is a measurement for the affinity of a drug to a receptor. The lower the value, the higher the affinity. 

For a detailed description of spectral map analysis (SMA), the reader is referred to Section 31.3.5. The method has been designed specifically for the study of drug-receptor interactions [37,44]. The interpretation of the resulting spectral map is different from that of the usual principal components biplot. The former is symmetric with respect to rows and columns, while the latter is not. In particular, the spectral map displays interactions between compounds and receptors. It shows which compounds are most specific for which receptors (or tests) and vice versa. This property will be illustrated by means of an analysis of data reporting on the binding affinities of various opioid analgesics to various opioid receptors [45,46]. In contrast with the previous approach, this application is not based on extra-thermodynamic properties, but is derived entirely from biological activity spectra. 

Drug Receptor Affinity Intrinsic Usual Sympathomimetic Dose Activity Range ... 

This view offers an explanation for the stereoselectivity of the phenylisopro-pylamines, i.e., the isomer that is more active is the one that presents least interference to the drug-receptor interaction. This idea would be consistent with the observation that the R enantiomers of the phenylisopropylamines have receptor affinity similar to their nonalpha-methylated homologs, and that the alpha-methyl of the S enantiomer of the amphetamines has a deleterious effect on affinity (72,78). There is no strongly compelling evidence in favor of either of the above hypotheses, however, and either is tenable. 

Compounds that exhibit roughly the same affinity to and j32 rsceptors independent of dosage such as nadolol, propranolol, pindolol, timolol, and labetalol (combined a- and j3-adrenoblocker) are classified as nonselective blockers. Drugs which in therapeutic doses have higher affinity to -receptors than to j32-receptors such as acebutol, atenolol, metoprolol, and esmolol, are called selective or cardioselective j3-adrenoblockers. 

Drug-receptor interactions often involve CT complex formation. Examples include the reactions of antimalarials with their receptors and of some antibiotics that intercalate with DNA. The CT energy is proportional to the ionization potential of the donor and the electron affinity of the receptor, but is usually no higher than about 30 kJ/mol. 

Xylometazoline and oxymetazoline are direct-acting agonists. These drugs have been used as topical decongestants because of their ability to promote constriction of the nasal mucosa. When taken in large doses, oxymetazoline may cause hypotension, presumably because of a central clonidine-like effect (see Chapter 11). Oxymetazoline has significant affinity fortx receptors. 

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