Carbachol – Structure , Synthesis , SAR , Mechanism , Uses

Carbachol

Structure – 

Carbachol is a choline analogue that is used as a medication to treat certain medical conditions. Its chemical structure is as follows:

Carbachol

The molecule contains a quaternary ammonium cation and an anionic carboxylate group. The carbon atom in the middle of the molecule is sp3-hybridized, with the nitrogen and oxygen atoms bonded to it in a tetrahedral geometry. The molecule is also symmetric, with two identical methyl groups and two identical hydrogen atoms on either side of the nitrogen atom.

Synthesis – 

Carbachol can be synthesized in a few different ways, but one common method involves the reaction of choline chloride with ethylene oxide and trimethylamine. Here are the basic steps involved in this synthesis:

  1. Mix choline chloride, ethylene oxide, and trimethylamine in a reaction flask.
  2. Heat the mixture to around 80-90°C and stir for several hours.
  3. The reaction will generate a white solid, which is the hydrochloride salt of carbachol. This can be isolated by filtration, washed with a solvent such as ether, and dried under vacuum.
  4. The carbachol hydrochloride salt can be converted to the free base form by treating it with a strong base such as sodium hydroxide. The resulting free base can be purified by recrystallization or other methods.

It’s worth noting that this is just one example of a carbachol synthesis, and there are other methods that may be used depending on the specific context and desired outcome.

 or 

The synthesis of Carbachol involves the reaction of choline chloride with ethylene oxide and trimethylamine. Here’s how it looks in terms of the molecular structure:

Step 1:

Carbachol

Step 2:

Carbachol

Step 3:

Carbachol

Step 4:

The resulting product, carbachol, is in its salt form, carbachol hydrochloride, which can be further converted to the free base form by treating it with a strong base such as sodium hydroxide.

SAR –

The SAR (Structure-Activity Relationship) of Carbachol refers to the relationship between the chemical structure of Carbachol and its biological activity. Carbachol is a cholinergic agonist, which means that it activates the same receptors as acetylcholine, a neurotransmitter in the nervous system. The SAR of Carbachol has been studied to optimize its pharmacological activity, selectivity, and safety. Here are some key features of the SAR of Carbachol:

  1. Quaternary ammonium group: The presence of a quaternary ammonium group (N⁺(CH3)3) is essential for the cholinergic activity of Carbachol, as it allows the molecule to interact with the acetylcholine receptor.
  2. Carbamate linkage: Carbachol has a carbamate linkage (-O-CO-NH-) that connects the choline and carbamoyl moieties. This linkage is important for maintaining the appropriate spatial orientation of the molecule for receptor binding.
  3. Methyl substitution: The methyl groups on the choline and carbamoyl moieties of Carbachol contribute to the molecule’s stability and lipophilicity, which affect its absorption and distribution in the body.
  4. Hydroxyl group: The hydroxyl group on the carbamoyl moiety of Carbachol enhances its water solubility and can affect its selectivity and potency for different subtypes of acetylcholine receptors.
  5. Ring size: it has a cyclohexane ring in the carbamoyl moiety, which has been found to be optimal for its cholinergic activity. Modifications to the ring size or structure can affect the molecule’s potency, selectivity, and metabolic stability.

Overall, the SAR of Carbachol highlights the importance of specific functional groups and stereochemistry for its cholinergic activity, and provides insights into how the molecule can be optimized for different pharmacological applications.

Mechanism –

The mechanism of action of it involves its ability to activate muscarinic and nicotinic acetylcholine receptors in the nervous system and other tissues. Here is a brief overview of the mechanism of action of Carbachol:

  1. Activation of muscarinic receptors: it binds to and activates muscarinic receptors, which are G protein-coupled receptors found in various tissues, including smooth muscle, cardiac muscle, and the central nervous system. Activation of muscarinic receptors leads to a variety of downstream effects, including smooth muscle contraction, decreased heart rate, increased glandular secretions, and modulation of neurotransmitter release.
  2. Activation of nicotinic receptors: it also activates nicotinic acetylcholine receptors, which are ligand-gated ion channels found in skeletal muscle, the autonomic ganglia, and the central nervous system. Activation of nicotinic receptors leads to depolarization of the cell membrane, which can trigger muscle contraction or modulate neuronal activity.
  3. Metabolism: it is rapidly metabolized by the enzyme acetylcholinesterase, which breaks it down into choline and acetic acid. This limits the duration of its pharmacological effects and prevents excessive activation of acetylcholine receptors.

Overall, the mechanism of action of Carbachol involves its ability to activate cholinergic receptors, which can have a wide range of physiological effects depending on the tissue and receptor subtype involved.

Uses

Carbachol has several medical and research applications due to its ability to activate cholinergic receptors. Here are some of the common uses of Carbachol:

  1. Ophthalmology: it is used as a topical agent to induce miosis (pupillary constriction) during intraocular surgery or as a diagnostic tool to assess pupillary function. It can also be used to reduce intraocular pressure in glaucoma by stimulating the muscarinic receptors on the ciliary muscle, which increases the outflow of aqueous humor.
  2. Gastrointestinal disorders: it can be used to treat gastrointestinal disorders such as gastric atony, ileus, and reflux by stimulating the muscarinic receptors in the smooth muscle of the gastrointestinal tract, which increases peristalsis and tone.
  3. Urinary disorders: it can be used to treat urinary retention or neurogenic bladder by stimulating the muscarinic receptors in the bladder wall, which increases detrusor muscle tone and promotes voiding.
  4. Neuroscience research: it is commonly used as a research tool to activate cholinergic receptors in neuronal and non-neuronal tissues, which can help elucidate the mechanisms underlying cholinergic neurotransmission and receptor function.
  5. Other uses: it can also be used to induce bronchoconstriction during pulmonary function testing, as a cardiac stimulant, and as a treatment for dry mouth or xerostomia.

It’s worth noting that the clinical use of Carbachol is limited due to its relatively short duration of action and potential side effects, such as bradycardia, hypotension, and bronchoconstriction. Therefore, it is typically used under the guidance of a healthcare provider and with close monitoring of vital signs.

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