Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor

Anthes, John C.; Gilchrest, Helen; Richard, Christian; Eckel, Stephen; Hesk, David; West, Robert; Williams, Shirley M.; Greenfeder, Scott; Billah, M. Motasim; Kreutner, William; Egan, Robert W.

doi:10.1016/s0014-2999(02)02049-6

Cited by 119 publications

(68 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first generation antagonist mepyramine (pyrilamine) competitively antagonizes histamine-induced increase in intracellular [Ca 21 ] and guinea pig ileum contraction, resulting in a right shift of the histamine concentration response curves without affecting the maximal response (Anthes et al, 2002;Slack et al, 2011b). In contrast, other antihistamines such as azelastine, desloratidine (Aerius; Merck Sharp & Dohme, Whitehouse Station, NJ),…”

Section: Examples For Biologic Discrimination By Different Ligand Resmentioning

confidence: 99%

“…, and ceterizine (Zyrtec; UCB, Brussels, Belgium) inhibited histamine-induced Ca 21 signaling and/or smooth muscle cell contraction in an apparently noncompetitive manner, resulting in an attenuated maximal response (Anthes et al, 2002;Slack et al, 2011a,b). Indeed, these insurmountable antagonists dissociated at least 70-fold more slowly from the H 1 R compared with mepyramine (Gillard et al, 2002;Anthes et al, 2002;Gillard and Chatelain, 2006;Slack et al, 2011b).…”

Section: Examples For Biologic Discrimination By Different Ligand Resmentioning

confidence: 99%

“…Indeed, these insurmountable antagonists dissociated at least 70-fold more slowly from the H 1 R compared with mepyramine (Gillard et al, 2002;Anthes et al, 2002;Gillard and Chatelain, 2006;Slack et al, 2011b).…”

Section: Examples For Biologic Discrimination By Different Ligand Resmentioning

confidence: 99%

See 2 more Smart Citations

Ligand Residence Time at G-protein–Coupled Receptors—Why We Should Take Our Time To Study It

et al. 2015

View full text Add to dashboard Cite

Over the past decade the kinetics of ligand binding to a receptor have received increasing interest. The concept of drug-target residence time is becoming an invaluable parameter for drug optimization. It holds great promise for drug development, and its optimization is thought to reduce off-target effects. The success of long-acting drugs like tiotropium support this hypothesis. Nonetheless, we know surprisingly little about the dynamics and the molecular detail of the drug binding process. Because protein dynamics and adaptation during the binding event will change the conformation of the protein, ligand binding will not be the static process that is often described. This can cause problems because simple mathematical models often fail to adequately describe the dynamics of the binding process. In this minireview we will discuss the current situation with an emphasis on G-protein-coupled receptors. These are important membrane protein drug targets that undergo conformational changes upon agonist binding to communicate signaling information across the plasma membrane of cells.

show abstract

Section: Examples For Biologic Discrimination By Different Ligand Resmentioning

confidence: 99%

Section: Examples For Biologic Discrimination By Different Ligand Resmentioning

confidence: 99%

See 1 more Smart Citation

Ligand Residence Time at G-protein–Coupled Receptors—Why We Should Take Our Time To Study It

et al. 2015

View full text Add to dashboard Cite

show abstract

“…After administration of ebastine, carebastine concentrations are 30-fold greater (Sastre, 2008;Shon et al, 2010). Furthermore, carebastine is intrinsically more potent at the H 1 receptor (Anthes et al, 2002). The exact values for plasma protein binding have not been reported as both parent and metabolite are highly bound and merely reported as .95%.…”

Section: A Drugs With Active Metabolites That Dominate the Activitymentioning

confidence: 99%

“…20). The intrinsic potency of desloratadine far exceeds that of the parent (Anthes et al, 2002), the free fraction is higher by 5-fold, and the circulating concentrations are also higher (Ramanathan et al, 2007). When these three factors are combined, it suggests that loratadine itself is responsible for none of the in vivo antihistaminic activity.…”

Section: A Drugs With Active Metabolites That Dominate the Activitymentioning

confidence: 99%

Pharmacologically Active Drug Metabolites: Impact on Drug Discovery and Pharmacotherapy

Obach

2013

Pharmacol Rev

137

View full text Add to dashboard Cite

Tight Binding Inhibition

Copeland¹

2013

Evaluation of Enzyme Inhibitors in Drug Discovery

View full text Add to dashboard Cite

Biochemical characterization of desloratadine, a potent antagonist of the human histamine H1 receptor

Cited by 119 publications

References 24 publications

Ligand Residence Time at G-protein–Coupled Receptors—Why We Should Take Our Time To Study It

Ligand Residence Time at G-protein–Coupled Receptors—Why We Should Take Our Time To Study It

Pharmacologically Active Drug Metabolites: Impact on Drug Discovery and Pharmacotherapy

Tight Binding Inhibition

Contact Info

Product

Resources

About