Paroxetine

Holliday, Stephen M.; Plosker, Greg L.

doi:10.2165/00002512-199303030-00008

Cited by 25 publications

(2 citation statements)

References 74 publications

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“…Neurokinin receptors are present in the inner ear and therefore represent a potential therapeutic target for tinnitus (209, 210). Paroxetine is an SSRI used to treat depression, obsessive-compulsive disorder and anxiety (211). …”

Section: Drug Therapy For Tinnitus: Pharmacological Studiesmentioning

confidence: 99%

Pharmacological treatments for tinnitus: New and old

Salvi¹,

Lobariñas²,

Sun³

2009

Drugs Fut

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Subjective tinnitus, the phantom ringing or buzzing sensation that occurs in the absence of sound, affects 12–14% of adults; in some cases the tinnitus is so severe or disabling that patients seek medical treatment. However, although the economic and emotional impact of tinnitus is large, there are currently no FDA-approved drugs to treat this condition. Clinical trials are now underway to evaluate the efficacy of N-methyl-d-aspartate (NMDA) and dopamine D2 antagonists, selective serotonin reuptake inhibitors (SSRIs), γ-aminobutyric acid (GABA) agonists and zinc dietary supplements. Previous off-label clinical studies, while not definitive, suggest that patients with severe depression may experience improvement in their tinnitus after treatment with antidepressants such as nortriptyline or sertraline. A small subpopulation of patients with what has been described as “typewriter tinnitus” have been shown to gain significant relief from the anticonvulsant carbamazepine. Preliminary studies with misoprostol, a synthetic prostaglandin E1 analogue, and sulpiride, a dopamine D2 antagonist, have shown promise. Animal behavioral studies suggest that GABA transaminase inhibitors and potassium channel modulators can suppress tinnitus. Additionally, improvements in tinnitus have also been noted in patients taking melatonin for significant sleep disturbances. Like other complex neurological disorders, one drug is unlikely to resolve tinnitus in all patients; therapies targeting specific subgroups are likely to yield the greatest success.

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Section: Drug Therapy For Tinnitus: Pharmacological Studiesmentioning

confidence: 99%

Pharmacological treatments for tinnitus: New and old

Salvi¹,

Lobariñas²,

Sun³

2009

Drugs Fut

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“…Sertraline is not applicable for single-dose administration because only 44% is absorbed after oral ingestion [ 45 ]. Paroxetine undergoes extensive first-pass metabolism, reducing its bioavailability to approximately 50% [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Selective serotonin reuptake inhibitors (SSRIs) prevent meta-iodobenzylguanidine (MIBG) uptake in platelets without affecting neuroblastoma tumor uptake

Blom

Meinsma²,

Rutgers

et al. 2020

EJNMMI Res

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Background: The therapeutic use of [ 131 I]meta-iodobenzylguanidine ([ 131 I]MIBG) is often accompanied by hematological toxicity, mainly consisting of persistent and severe thrombocytopenia. While MIBG accumulates in neuroblastoma cells via selective uptake by the norepinephrine transporter (NET), the serotonin transporter (SERT) is responsible for cellular uptake of MIBG in platelets. In this study, we have investigated whether pharmacological intervention with selective serotonin reuptake inhibitors (SSRIs) may prevent radiotoxic MIBG uptake in platelets without affecting neuroblastoma tumor uptake. Methods: To determine the transport kinetics of SERT for [ 125 I]MIBG, HEK293 cells were transfected with SERT and uptake assays were conducted. Next, a panel of seven SSRIs was tested in vitro for their inhibitory potency on the uptake of [ 125 I]MIBG in isolated human platelets and in cultured neuroblastoma cells. We investigated in vivo the efficacy of the four best performing SSRIs on the accumulation of [ 125 I]MIBG in nude mice bearing subcutaneous neuroblastoma xenografts. In ex vivo experiments, the diluted plasma of mice treated with SSRIs was added to isolated human platelets to assess the effect on [ 125 I]MIBG uptake. Results: SERT performed as a low-affinity transporter of [ 125 I]MIBG in comparison with NET (K m = 9.7 μM and 0.49 μM, respectively). Paroxetine was the most potent uptake inhibitor of both serotonin (IC 50 = 0.6 nM) and MIBG (IC 50 = 0.2 nM) in platelets. Citalopram was the most selective SERT inhibitor of [ 125 I]MIBG uptake, with high SERT affinity in platelets (IC 50 = 7.8 nM) and low NET affinity in neuroblastoma cells (IC 50 = 11.940 nM). The in vivo tested SSRIs (citalopram, fluvoxamine, sertraline, and paroxetine) had no effect on [ 125 I]MIBG uptake levels in neuroblastoma xenografts. In contrast, treatment with desipramine, a NET selective inhibitor, resulted in profoundly decreased xenograft [ 125 I]MIBG levels (p < 0.0001). In ex vivo [ 125 I]MIBG uptake experiments, 100-and 34-fold diluted murine plasma of mice treated with citalopram added to isolated human platelets led to a decrease in MIBG uptake of 54-76%, respectively.

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Selective in vitro and in vivo binding of [125I]ADAM to serotonin transporters in rat brain

Choi

Hou

Oya

et al. 2000

Synapse

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An improved iodinated tracer, ADAM (2‐((2‐((dimethylamino)methyl)‐ phenyl)thio)‐5‐iodophenylamine) for imaging serotonin transporters (SERT) with single photon emission computerized tomography (SPECT), was prepared and characterized. Scatchard analysis of saturation binding of [125I]ADAM to rat frontal cortical membrane homogenates gave a Kd value of 0.15 ± 0.03 nM and a Bmax value of 194 ± 65 fmol/mg protein. Biodistribution of [125I]ADAM in rat brain after an iv injection showed a high specific binding in the regions of hypothalamus, cortex, striatum, and hippocampus, where SERT are concentrated and the specific binding peaked at 120–240 min postinjection [(hypothalamus‐cerebellum)/cerebellum = 4.3 at 120 min post‐iv injection]. Moreover, the specific hypothalamic uptake was blocked by pretreatment with SERT selective competing drugs, such as paroxetine and (+)McN5652, while other noncompeting drugs, such as ketanserin, raclopride, and methylphenidate, showed no effect. The radioactive material recovered from rat brain homogenates at 120 min after [125I]ADAM injection showed primarily the original compound (>90%), a good indication of in vivo stability in the brain tissues. Both male and female rats showed similar and comparable organ distribution pattern and regional brain uptakes. Ex vivo autoradiograms of rat brain sections (120 min after iv injection of [125I]ADAM) showed intense labeling in several regions (olfactory tubercle, lateral septal nucleus, hypothalamic and thalamic nuclei, globus pallidus, central gray, superior colliculus, substantia nigra, interpeduncular nucleus, dorsal and median raphes, and locus coerulus), which parallel known SERT density. These results strongly suggest that the novel tracer ADAM is superior to the congers (i.e., IDAM) reported previously. When labeled with I‐123, ADAM will be an improved and useful SPECT imaging agent for SERT in the brain. Synapse 38:403–412, 2000. © 2000 Wiley‐Liss, Inc.

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Paroxetine

Cited by 25 publications

References 74 publications

Pharmacological treatments for tinnitus: New and old

Pharmacological treatments for tinnitus: New and old

Selective serotonin reuptake inhibitors (SSRIs) prevent meta-iodobenzylguanidine (MIBG) uptake in platelets without affecting neuroblastoma tumor uptake

Selective in vitro and in vivo binding of [125I]ADAM to serotonin transporters in rat brain

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