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Related Concept Videos

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic antagonists are called...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Cholinergic Antagonists: Pharmacokinetics01:24

Cholinergic Antagonists: Pharmacokinetics

Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and the conjunctiva.
Cholinergic Antagonists: Therapeutic Uses01:26

Cholinergic Antagonists: Therapeutic Uses

Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:    
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action01:17

Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action

Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Cholinergic Antagonists: Pharmacological Actions01:28

Cholinergic Antagonists: Pharmacological Actions

Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...

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Related Experiment Video

Updated: Jun 4, 2026

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
09:59

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein

Published on: March 9, 2015

Zwitterionic CRTh2 antagonists.

Tim Luker1, Roger Bonnert, Stuart W Paine

  • 1Department of Medicinal Chemistry, AstraZeneca R & D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, United Kingdom. tim.luker@astrazeneca.com

Journal of Medicinal Chemistry
|March 2, 2011
PubMed
Summary
This summary is machine-generated.

Researchers developed novel zwitterions as potent and selective antagonists for the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2). These compounds show promise for further in vivo studies due to optimized properties and high potency.

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
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Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
09:59

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Area of Science:

  • Medicinal Chemistry
  • Pharmacology

Background:

  • The chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2) is a key target in inflammatory diseases.
  • Selective antagonists for CRTh2 are needed for therapeutic intervention.

Purpose of the Study:

  • To discover and optimize novel zwitterionic CRTh2 antagonists.
  • To develop compounds with improved physicochemical properties and reduced off-target effects.

Main Methods:

  • Virtual screening to identify a lead compound.
  • Structure-activity relationship studies and lead optimization.
  • Modification of side chains and acidic moieties.
  • Assessment of physicochemical properties (log D, MWt, HBA), metabolic stability, hERG activity, and permeability.

Main Results:

  • A novel series of potent and selective CRTh2 antagonists was synthesized.
  • Lead compound 2 was identified via virtual screening.
  • Optimization yielded compounds with maintained CRTh2 potency, low metabolism, and acceptable safety profiles.
  • A single methyl group on the piperazine ring significantly enhanced potency.

Conclusions:

  • Novel zwitterionic CRTh2 antagonists were successfully developed.
  • Optimized compounds possess suitable properties for progression into in vivo studies.
  • This work provides a promising foundation for developing new CRTh2-targeted therapies.