Escitalopram

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Cat Number

API128196010

CAS Number

128196-01-0

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CAS Number

128196-01-0

Storage

Powder: -20℃ for 3 years. In solvent: -80℃ for 1 year.

Synonyms

(1R)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-3H-isobenzofuran-5-carbonitrile

Molecular Formula

C20H21FN2O

Molecular Weight

324.39

Smiles

C(CCN(C)C)[C@@]1(C=2C(CO1)=CC(C#N)=CC2)C3=CC=C(F)C=C3

Appearance

Off-white powder

Boiling Point

428.3±45.0 ℃

Relative Density

1.18

pKa

9.57±0.28

General Description

Escitalopram is a selective Serotonin Reuptake Inhibitor (SSRI). It has a 30-fold higher binding affinity for the serotonin transporter compared with the R(-)-enantiomer. It has also shown selectivity for dopamine transporters (DAT) and norepinephrine transporters (NET). As a widely used antidepressant, Escitalopram has a single metabolic pathway, contributing to fewer side effects and a broad range of combined uses. Compared with tricyclic antidepressants, it is preferred for depressed patients with tardive dyskinesia.

Mechanism of Action

The antidepressant activity of Escitalopram is thought to be linked to its increased serotonergic activity in the CNS. Serotonin is a neurotransmitter that carries signals between nerve cells in the brain and after transmission, it is usually reabsorbed into the nerve cells from which it was released. Escitalopram prevents the re-uptake of serotonin. This in turn increases the quantity of available serotonin in the synaptic cleft. There are 2 binding sites on the serotonin transporter protein, with most drugs only binding to the primary site. It has been shown that Escitalopram binds to both the primary site as well as the allosteric site. This dual action mechanism on the serotonin transporter results in the rapid onset of action.

Application

Escitalopram is used in the treatment of moderate to severe depression (endogenous and non-endogenous depression), severe depression and generalized anxiety disorders. In addition to depression and anxiety disorders, Escitalopram also has additional therapeutic value as it is effective at reducing ethanol uptake by alcoholics.

As an SSRI, Escitalopram is an antagonist of the serotonin transporter (SERT), which is an integral membrane protein that serves to clear synaptic serotonin from the cleft by reuptake into presynaptic neurons. By blocking SERT, Escitalopram inhibits the reuptake of serotonin into the neuron, prolonging its activity in the synapse and thus increasing serotonergic neurotransmission.
he study revealed that Escitalopram operates in a unique dual-binding mode. In addition to the primary binding site, Escitalopram also interacts with an allosteric site located in the transporter's external vestibule. The allosteric binding is believed to retard dissociation from the central binding site, thereby stabilizing Escitalopram's presence and prolonging its inhibitory action. This dual-binding mechanism may underlie Escitalopram's clinical superiority and potentially rapid onset of action compared to other SSRIs.
Escitalopram's high selectivity for SERT, coupled with this unique dual-binding mechanism, contributes to its efficacy and tolerability. The discovery of the allosteric site also provides a new target for the development of highly efficacious antidepressants, demonstrating how structural biology can inform the rational optimization of therapeutics for complex neuropsychiatric diseases.

Fig. 1 Mechanism of action of Escitalopram in treating antidepressant. (Caron M G.; et al. 2019)

References

Caron M G, et al. Antidepressants at work. Nature, 2016, 532(7599): 320-321.

Jawad M et al. formulated and developed a poloxamer-based thermosensitive gel system containing escitalopram-loaded nanostructured lipid carriers (ESC-NLCs gel) for nose-to-brain drug delivery. The ESC-NLCs formulation was optimized by software and then incorporated into a poloxamer-based thermosensitive gel system. Subsequently, the developed formulation was thoroughly evaluated by in vitro release, ex vivo permeation, and in vivo pharmacokinetic (brain and plasma) analysis along with behavioral assessment in lipopolysaccharide (LPS)-induced depressed rats followed by immunohistochemical study of the hippocampal and cortical areas.
In the animal model, ESC-NLCs gel treatment alleviated depressive-like behaviors and decreased the expression of neuroinflammatory markers (NF-κB and TNF-α) in the hippocampus and cortex. The study shows that the ESC-NLCs gel system allows sustained release of the drug and with enhanced bioavailability, leads to antidepressant effects via nose-to-brain delivery in an animal model.

Fig. 2 Escitalopram-loaded NLC thermosensitive gel for nose-to-brain delivery. (Jawad M.; et al. 2024)

References

Jawad M, et al. Nose to brain delivery of escitalopram-loaded nano-structured lipid carriers thermosensitive gel: Formulation, physiochemical, pharmacokinetic and pharmacodynamics evaluation. Journal of Drug Delivery Science and Technology, 2024, 97: 105800.