Carbachol is a cholinergic agonist that acts on both muscarinic and nicotinic receptors. It is often used in ophthalmology to stimulate mi...
Carbachol is a cholinergic agonist that acts on both muscarinic and nicotinic receptors. It is often used in ophthalmology to stimulate miosis (pupillary constriction) and reduce intraocular pressure. Understanding the structure-activity relationship (SAR) of carbachol can provide insights into the modifications that can be made to its structure to optimize its pharmacological properties. Here is an overview of the SAR of carbachol:
Choline (R2):
The choline moiety in carbachol is essential for receptor binding and activation, similar to acetylcholine. Modifications to the choline structure can influence the affinity and selectivity of carbachol for both muscarinic and nicotinic receptors.
Ester Linkage:
The ester linkage between the acetyl group and choline in carbachol is crucial for its stability and enzymatic hydrolysis by cholinesterases. Alterations to the ester linkage can impact the pharmacokinetics and duration of action of carbachol.
Hydroxyl Group (R3):
Carbachol contains a hydroxyl group at position R3, which is absent in acetylcholine. This hydroxyl group contributes to the hydrogen bonding interactions and can influence the receptor binding affinity and activity of carbachol.
Spacer Length (Carbon Chain):
The carbon chain connecting the choline and ester groups in carbachol can be modified to vary the spacer length. Changes in the spacer length can affect the conformation, flexibility, and overall pharmacological activity of carbachol.
Substituents on Choline Nitrogen:
Modifications to the substituents on the choline nitrogen can impact the lipophilicity, receptor selectivity, and metabolic stability of carbachol. Different substituents can be introduced to enhance or alter the pharmacological profile of the compound.
Substituents on Carbamic Acid:
Carbachol contains a carbamic acid moiety, which can be modified with different functional groups. These modifications can influence the receptor binding affinity, selectivity, and overall potency of carbachol.
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