Determination of sertraline in rat plasma by <scp>HPLC</scp> and fluorescence detection and its application to <i>in vivo</i> pharmacokinetic studies

Melis, Virginia; Usach, Iris; Peris, José-Esteban

doi:10.1002/jssc.201200586

Cited by 15 publications

(9 citation statements)

References 35 publications

(34 reference statements)

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“…Once-daily administration of CBD, STR, CBD plus STR or the corresponding vehicles (from 15:00 to 17:00 h) was carried out between weeks 11 and 14 of the model. A latency time of 90 (CBD) and/or 60 (STR) minutes was left before any behavioral evaluation according to previously published pharmacokinetics data ( Deiana et al, 2012 ; Melis et al, 2012 ). Drug doses were selected according to prior literature ( Wang et al, 2006 ; Blessing et al, 2015 ) and to preliminary results obtained with CBD in our laboratory (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

2021

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This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. The effects of the administration of CBD (20 mg/kg, i.p.) and/or STR (10 mg/kg, p.o.) were analyzed on behavioral and gene expression changes induced by the model of PTSD. Gene expression alterations of targets related with stress regulation, endocannabinoid and serotonergic systems were analyzed by real-time PCR. The results revealed an increased and long-lasting fear-related memory and anxiety-like behaviors in mice exposed to the animal model of PTSD. Treatment with CBD improved these behaviors in PTSD animals, effects that were significantly potentiated when combined with STR. Gene expression analyses revealed a long-term increase of corticotropin releasing factor (Crf) that was significantly normalized with the combination CBD plus STR. Cannabinoid receptors (Cnr1 and Cnr2) were up regulated in PTSD mice whereas the serotonin transporter (Slc6a4) was reduced. Interestingly, CBD and STR alone or combined induced a significant and marked increase of Slc6a4 gene expression. These results point out the cooperative action of the combination CBD plus STR to enhance fear extinction and reduce anxiety-like behaviors, normalizing gene expression alterations in this animal model of PTSD and suggesting that the combination of CBD with STR deserves to be further explored for the treatment of patients with PTSD.

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Section: Methodsmentioning

confidence: 99%

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

2021

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“…Daily STL doses range from 50 to 200 mg and display linear pharmacokinetics in humans, with steady state plasma concentrations ranging between 0.18 and 0.82 μ m . The plasma levels of STL in rats after the oral administration of a single 16.7 mg/kg dose are 0.20–0.51 μ m . This range is below the minimum perfusion concentration we selected for the in situ study, which was 1 μ m .…”

Section: Discussionmentioning

confidence: 99%

In-vitro and in situ assessment of the efflux of five antidepressants by breast cancer resistance protein

Feng

Zheng

Tang

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Antidepressants need to penetrate the blood-brain barrier (BBB) to exert their functions in the central nervous system. Breast cancer resistance protein (BCRP), an efflux transporter abundantly expressed in the BBB, prevents the accumulation of many drugs in the brain. This study aimed to identify whether five commonly used antidepressants (sertraline, duloxetine, fluoxetine, amitriptyline and mirtazapine) are BCRP substrates. Methods A combination of bidirectional transport and intracellular accumulation experiments was conducted on BCRP-overexpressing MDCKII and wildtype (WT) cells, and in situ brain perfusion was conducted in rats. Key findings The bidirectional transport study revealed that the net efflux ratio (NER) of sertraline reached 2.08 but decreased to 1.06 when co-incubated with Ko143, a selective BCRP inhibitor. Conversely, the other four antidepressants did not appear to be BCRP substrates, due to their low NER values (<1.5). The accumulation of sertraline in MDCKII-BCRP cells was significantly lower than that in MDCKII-WT cells. The presence of Ko143 significantly increased the sertraline accumulation in MDCKII-BCRP cells but not in MDCKII-WT cells. Brain perfusion showed that the permeability of 1 and 5 lM sertraline was significantly higher in the presence of Ko143. Conclusions Taken together, BCRP is involved in sertraline efflux.

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“…Most SSRIs, including sertraline and citalopram, have a half-life of 24–36 h in humans. In rats, orally administered sertraline has been reported to have a half-life of 4 h [ 31 ], remarkably shorter than in humans. On the other hand, the half-life of citalopram in rats is 1–1.6 h when the drug is administered intraperitoneally; lower bioavailability is expected for the oral route, due to increased biotransformation in this animal model [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Sertraline and Citalopram Actions on Gut Barrier Function

et al. 2020

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Introduction Disruption of intestinal barrier is a key component to various diseases. Whether barrier dysfunction is the cause or effect in these situations is still unknown, although it is believed that translocation of luminal content may initiate gastrointestinal or systemic inflammatory disorders. Since trauma- or infection-driven epithelial permeability depends on Toll-like receptor (TLR) activity, inhibition of TLR signaling has been proposed as a strategy to protect intestinal barrier integrity after infection or other pathological conditions. Recently, selective serotonin recapture inhibitors including sertraline and citalopram were shown to inhibit TLR-3 activity, but the direct effects of these antidepressant drugs on the gut mucosa barrier remain largely unexplored. Materials and methods To investigate this, two approaches were used: first, ex vivo studies were performed to evaluate sertraline and citalopram-driven changes in permeability in isolated intestinal tissue. Second, both compounds were tested for their preventive effects in a rat model of disrupted gut barrier, induced by a low protein (LP) diet. Results Only sertraline was able to increase transepithelial electrical resistance in the rat colon both when used in an ex vivo (0.8 μg/mL, 180 min) or in vivo (30 mg/kg p.o., 20 days) fashion. However, citalopram (20 mg/kg p.o., 20 days), but not sertraline, prevented the increase in phospho–IRF3 protein, a marker of TLR-3 activation, in LP-rat ileum. Neither antidepressant affected locomotion, anxiety-like behaviours or stress-induced defecation. Conclusion Our data provides evidence to support the investigation of sertraline as therapeutic strategy to protect intestinal barrier function under life-threatening situations or chronic conditions associated with gut epithelial disruption.

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Determination of sertraline in rat plasma by HPLC and fluorescence detection and its application to in vivo pharmacokinetic studies

Cited by 15 publications

References 35 publications

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD

In-vitro and in situ assessment of the efflux of five antidepressants by breast cancer resistance protein

Sertraline and Citalopram Actions on Gut Barrier Function

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