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Related Concept Videos

Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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

Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
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...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
Cholinergic Receptors: Nicotinic01:15

Cholinergic Receptors: Nicotinic

Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...

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A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
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7-Azaindole derivatives as potential partial nicotinic agonists.

Axel R Stoit1, Arnold P den Hartog, Harry Mons

  • 1Solvay Pharmaceuticals, Research Laboratories, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. axel.stoit@solvay.com

Bioorganic & Medicinal Chemistry Letters
|November 17, 2007
PubMed
Summary

Researchers explored 7-azaindoles as partial agonists for alpha4beta2 nicotinic acetylcholine receptors (nAChRs). Compound 30A shows promise for cognitive disorders and smoking cessation due to its binding affinity and partial agonist activity.

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Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
10:04

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

Published on: October 29, 2012

Area of Science:

  • Medicinal Chemistry
  • Neuroscience
  • Pharmacology

Background:

  • Nicotinic acetylcholine receptors (nAChRs), particularly the alpha4beta2 subtype, are implicated in cognitive functions and nicotine addiction.
  • Developing selective modulators of nAChRs is crucial for therapeutic interventions.

Purpose of the Study:

  • To synthesize and evaluate novel 7-azaindole derivatives as potential partial agonists of the alpha4beta2 nAChR.
  • To identify lead compounds with favorable binding affinity and functional activity for potential therapeutic applications.

Main Methods:

  • Synthesis of three series of 7-azaindole derivatives.
  • Assessment of binding affinity to rat brain neuronal nicotinic receptors.
  • Evaluation of functional activity as partial agonists at the alpha4beta2 nAChR.

Main Results:

  • Compound (+)-51 demonstrated high binding affinity with a Ki of 10 nM.
  • Compound 30A exhibited moderate binding affinity and significant partial agonist potency.
  • The 7-azaindole scaffold is a viable starting point for developing nAChR modulators.

Conclusions:

  • 7-azaindole derivatives are promising candidates for modulating alpha4beta2 nAChR activity.
  • Compound 30A represents a potential lead compound for treating cognitive deficits and aiding smoking cessation.
  • Further optimization of 7-azaindole derivatives could yield novel therapeutics for neurological disorders.