シタロプラム

Q1: What is the primary mechanism of action of Citalopram?

A1: Citalopram primarily acts by inhibiting the serotonin transporter (SERT), a protein responsible for the reuptake of serotonin from the synaptic cleft back into the presynaptic neuron. This inhibition effectively increases the concentration of serotonin in the synapse, enhancing serotonergic neurotransmission. [, , ]

Q2: Does Citalopram interact with other molecular targets besides SERT?

A2: While Citalopram exhibits high selectivity for SERT, research indicates it can also interact with other molecular targets, including certain potassium channels. Notably, it inhibits TREK-1, TREK-2, and TRESK potassium channels, which are involved in regulating neuronal excitability. []

Q3: How does Citalopram's S-enantiomer, Escitalopram, differ in its interaction with SERT?

A3: Escitalopram demonstrates a higher affinity for SERT compared to the racemic Citalopram mixture. This difference in binding affinity contributes to its potentially faster onset of action and greater efficacy. [, , ]

Q4: What is the role of the R-enantiomer of Citalopram?

A4: The R-enantiomer of Citalopram, while not directly contributing to the therapeutic effect, has been shown to potentially inhibit the binding of the S-enantiomer to SERT, thereby potentially reducing its efficacy. []

Q5: How does chronic Citalopram treatment affect the adrenal gland's response to adrenocorticotropic hormone (ACTH)?

A5: Research suggests that chronic Citalopram treatment does not appear to sensitize the adrenal gland to ACTH in rats. While Citalopram-treated rats can elicit a corticosterone response to stress, this response is not accompanied by increased ACTH levels, suggesting alternative mechanisms may be involved. []

Q6: Has Citalopram been investigated for potential anti-cancer effects?

A6: Research indicates that Citalopram exhibits anti-proliferative activity against certain cancer cell lines, including the liver hepatocellular carcinoma cell line HepG2. This effect has been linked to the induction of apoptosis through mechanisms involving cytochrome C release and reactive oxygen species (ROS)-dependent activation of nuclear factor-κB (NF-κB). []

Q7: How do structural modifications of the Citalopram molecule influence its activity and selectivity?

A7: While the provided research papers do not extensively cover specific structural modifications and their impact, it is generally understood that even subtle alterations to the Citalopram molecule can significantly affect its binding affinity for SERT and other targets, potentially altering its pharmacological profile. This emphasizes the importance of SAR studies in drug development to optimize efficacy and minimize off-target effects. [General knowledge based on the field of medicinal chemistry]

Q8: How is Citalopram metabolized in the body?

A9: Citalopram is primarily metabolized in the liver by cytochrome P450 (CYP) enzymes, mainly CYP2C19, with CYP3A4 and CYP2D6 playing minor roles. The primary metabolite, desmethylcitalopram, also exhibits pharmacological activity. [, , , ]

Q9: How does CYP2C19 genotype influence Citalopram metabolism and potential for adverse effects?

A10: Individuals classified as "slow metabolizers" due to genetic variations in the CYP2C19 gene may experience higher plasma concentrations of Citalopram compared to "normal metabolizers" receiving the same dose. This can lead to an increased risk of side effects and requires careful dose adjustments. [, , , ]

Q10: What in vitro models have been used to study the effects of Citalopram on neural cells?

A12: Rat PC12 cells have been utilized as an in vitro model to investigate the neuroprotective potential of Citalopram. Studies demonstrated that Citalopram exhibited anti-apoptotic effects on serum-deprived PC12 cells, potentially mediated by the upregulation of brain-derived neurotrophic factor (BDNF). []

Q11: What animal models have been used to investigate the effects of Citalopram on depression-related behaviors?

A13: The rat chronic mild stress (CMS) model, a well-established animal model of depression, has been employed to evaluate the antidepressant-like effects of Citalopram. Results showed that Citalopram effectively reversed CMS-induced behavioral deficits, further supporting its therapeutic potential. []

Q12: How does the time to response for Citalopram compare to other antidepressants in the rat CMS model?

A14: In the rat CMS model, Citalopram exhibited a faster onset of action compared to the tricyclic antidepressant imipramine and the SSRI fluoxetine, indicating potential advantages in terms of treatment response time. []

Q13: What cardiac effects have been associated with Citalopram, and what precautions are recommended?

A15: Citalopram, particularly at higher doses or in individuals with certain risk factors, has been associated with QTc interval prolongation on electrocardiograms (ECGs), a risk factor for potentially fatal ventricular arrhythmias like torsade de pointes. Regulatory bodies recommend dose adjustments and careful monitoring in patients with a history of cardiac conditions, electrolyte disturbances, or those taking medications known to prolong the QTc interval. [, , , ]

Q14: Is there a reliable ECG marker to predict the risk of ventricular arrhythmias in Citalopram intoxication?

A16: Research suggests that the QRS/QTc ratio, a novel ECG marker, shows promise in predicting ventricular arrhythmia risk in Citalopram intoxication. Patients experiencing ventricular arrhythmias exhibited significantly lower QRS/QTc ratios compared to those without arrhythmias. []

Q15: How does Escitalopram compare to other antidepressants in terms of efficacy and tolerability?

A17: Meta-analyses of clinical trials suggest that Escitalopram demonstrates comparable or superior efficacy to other SSRIs, such as Citalopram, Fluoxetine, Paroxetine, and Sertraline, in treating major depressive disorder. It may also have a more favorable tolerability profile compared to some other antidepressants. [, , , , ]

Q16: Are there non-pharmacological alternatives or adjunctive therapies for depression that can be considered?

A16: Yes, various non-pharmacological interventions, such as cognitive behavioral therapy (CBT), interpersonal therapy, and other forms of psychotherapy, have proven effective in treating depression. These therapies can be used alone or in conjunction with medication, depending on the individual patient's needs and preferences. [General knowledge based on the field of psychiatry]

Q17: What analytical methods are commonly employed for the quantification of Citalopram and its metabolites in biological samples?

A19: High-performance liquid chromatography (HPLC) coupled with various detection methods, such as ultraviolet (UV) detection or mass spectrometry (MS), is widely used for the accurate and sensitive quantification of Citalopram and its metabolites in plasma and other biological matrices. [, , ]

Q18: What sample preparation techniques are often used prior to HPLC analysis of Citalopram in biological samples?

A20: Solid-phase extraction (SPE) is a common sample preparation technique used to extract and purify Citalopram from biological matrices, such as plasma, prior to HPLC analysis. This technique helps to remove interfering compounds and concentrate the analyte of interest, improving the sensitivity and reliability of the analysis. [, ]

Q19: Have thin-layer chromatography (TLC) methods been explored for the analysis of Citalopram?

A21: Yes, TLC coupled with densitometric analysis has been investigated as a potential method for the simultaneous analysis of Citalopram and other centrally acting serotonin reuptake inhibitors. []