Exuber 10

Exuber 10 Mechanism of Action

escitalopram

Manufacturer:

Cadila Healthcare

Distributor:

Zydus Healthcare Phils
Full Prescribing Info
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Pharmacology: Pharmacodynamics: The mechanism of antidepressant action of Escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). In vitro and in vivo studies in animals suggest that Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na+, K+, Cl-, and Ca++ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.
Pharmacokinetics: The single and multiple-dose pharmacokinetics of Escitalopram are linear and dose proportional in a dose range of 10 to 30 mg/day. Biotransformation of Escitalopram is mainly hepatic, with a mean terminal half-life of about 27 to 32 hours. With once-daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of Escitalopram in plasma in young healthy subjects was 2.2 to 2.5 times the plasma concentrations observed after a single dose.
Absorption and Distribution: Following a single oral dose (20 mg tablet) of Escitalopram, peak blood levels occur at about 5 hours. Absorption of escitalopram is not affected by food. The absolute bioavailability of citalopram is about 80% relative to an intravenous dose, and the volume of distribution of citalopram is about 12 L/kg. The binding of escitalopram to human plasma proteins is approximately 56 %.
Metabolism and Elimination: Following oral administrations of Escitalopram, the fraction of drug recovered in the urine as Escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively. The oral clearance of Escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance. Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged escitalopram is the predominant compound in plasma. At steady state, the concentration of the Escitalopram metabolite S-DCT in plasma is approximately one-third that of Escitalopram. The level of S-DDCT was not detectable in most subjects. In vitro studies show that Escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of Escitalopram do not contribute significantly to the antidepressant actions of Escitalopram. S-DCT and S-DDCT also have no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Na+, K+, Cl-, and Ca++ channels.
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