High Occupancy of Sigma-1 Receptors in the Human Brain after Single Oral Administration of Fluvoxamine: A Positron Emission Tomography Study Using [11C]SA4503

@article{Ishikawa2007HighOO,
  title={High Occupancy of Sigma-1 Receptors in the Human Brain after Single Oral Administration of Fluvoxamine: A Positron Emission Tomography Study Using [11C]SA4503},
  author={M. Ishikawa and K. Ishiwata and K. Ishii and Y. Kimura and M. Sakata and M. Naganawa and K. Oda and Ryousuke Miyatake and M. Fujisaki and E. Shimizu and Y. Shirayama and M. Iyo and K. Hashimoto},
  journal={Biological Psychiatry},
  year={2007},
  volume={62},
  pages={878-883}
}
BACKGROUND Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. METHODS A dynamic positron emission… Expand
High occupancy of sigma1 receptors in the human brain after single oral administration of donepezil: a positron emission tomography study using [11C]SA4503.
TLDR
It is demonstrated that donepezil binds to sigma1 receptors in the living human brain at therapeutic doses and sigma2 receptors may be implicated in the pharmacological mechanism ofdonepezil in the human brain. Expand
High occupancy of s 1 receptors in the human brain after single oral administration of donepezil: a positron emission tomography
The acetylcholinesterase (AChE) inhibitor donepezil is also a s1 receptor agonist. We examined whether donepezil binds to s1 receptors in the living human brain after a single oral administration.Expand
Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine
TLDR
The in vivo properties of [18F]fluspidine offer a high potential of this radiotracer for neuroimaging and quantitation of σ1 receptors in vivo and metabolic stability both in vitro and in animal experiments. Expand
Roles of σ1 receptors in the mechanisms of action of CNS drugs
Accumulating evidence suggests that σ1 receptors play a role in the mechanisms of action of some therapeutic drugs, such as the selective serotonin reuptake inhibitors (SSRIs), donepezil, andExpand
Sigma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders.
TLDR
The role of s Sigma-1 receptors in the mechanistic action of some SSRIs, donepezil, neurosteroids, and ifenprodil, and the clinical implications for sigma-1 receptor agonists are discussed. Expand
Re-evaluation of in vivo selectivity of [(11)C]SA4503 to σ(1) receptors in the brain: contributions of emopamil binding protein.
TLDR
An in vivo blocking experiment using high-affinity EBP and ρ(1) selective blocker confirmed the σ(1)-selective binding of [(11)C]SA4503 in the brain. Expand
The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases
TLDR
The function of sigma-1 receptors is reviewed and their role in the pathophysiology of neuropsychiatric diseases is attempted to be reinterpreted based on their new description as "receptor chaperones". Expand
Application of [¹¹C]SA4503 to selection of novel σ₁ selective agonists.
TLDR
This technique is a practical and high-throughput method that can directly evaluate blood-brain barrier permeability, receptor binding, and bioavailability of drug candidates at the same time. Expand
Positron Emission Tomography Imaging Evaluation of a Novel 18F-Labeled Sigma-1 Receptor Radioligand in Cynomolgus Monkeys.
TLDR
It is demonstrated that [18F]FBFP is a highly promising PET radioligand for imaging and quantification of σ1 receptors in humans. Expand
Brain Imaging of Sigma Receptors
TLDR
Drug-loading [11C]SA4503-positron emission tomography studies using therapeutic drugs for neurological and neuropsychiatric disorders have shown that some of the drugs had an affinity for sigma1 receptors in the human brain in addition to their main targets. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 48 REFERENCES
A feasibility study of [11C]SA4503-PET for evaluating sigma1 receptor occupancy by neuroleptics: The binding of haloperidol to sigma1 and dopamine D2-like receptors
TLDR
It is concluded that [11C]SA4503-PET can be used for evaluating the σlR occupancy rates by neuroleptics or other drugs. Expand
Mapping of human cerebral sigma1 receptors using positron emission tomography and [11C]SA4503
TLDR
The objective of this study was to establish the kinetic analysis for mapping sigma(1) receptors (sigma1Rs) in the human brain by positron emission tomography (PET) with [(11)C]SA4503, a recently developed radioligand with high and selective affinity for sigma1 Rs. Expand
Sigma1 and dopamine D2 receptor occupancy in the mouse brain after a single administration of haloperidol and two dopamine D2-like receptor ligands.
TLDR
This study investigates sigma(1) and dopamine D(2) receptor occupancy in mouse brain after a single injection of haloperidol, nemonapride, or spiperone using [(11)C]SA4503 and [(11]C]raclopride, respectively, to find out if these compounds would be applicable to the investigation of sigma (1) receptors occupancy of antispychotic drugs using PET. Expand
In vivo evaluation of [11C]SA4503 as a PET ligand for mapping CNS sigma1 receptors
TLDR
In the blocking study with one of four sigma receptor ligands including haloperidol, (+)-pentazocine, SA4503, and (-)-pentAZocine (in the order of their affinity for sigma(1) receptor subtype), SA 4503 and haloperids significantly reduced the brain uptake of [(11)C]SA4503 to approximately 30% of the control, but the other two benzomorphans did not. Expand
High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography.
TLDR
Clinical doses of clomipramine and fluvoxamine occupied approximately 80% of 5- HTT, and dose escalation would have minimal effect on 5-HTT blockade, and occupational occupancy increased in a curvilinear manner. Expand
Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain.
TLDR
It is suggested that sigma receptors (sigma 1 site) may play, in some way, a role in the actions of selective serotonin reuptake inhibitors. Expand
Binding properties of SA4503, a novel and selective σ1 receptor agonist
Abstract The binding profiles of SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), a novel σ receptor ligand, to σ1 and σ2 receptor subtypes in guinea pig and ratExpand
Measuring receptor occupancy with PET.
  • A. Waarde
  • Biology, Medicine
  • Current pharmaceutical design
  • 2000
TLDR
This review focuses on the monitoring of drug-receptor interactions in patients and healthy volunteers with PET, and measurements of plasma pharmacokinetics can be combined with images of receptor occupancy and be quantitatively related to pharmacologic effects which are induced in the same subjects. Expand
Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals.
TLDR
The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of s resolution agonists as novel therapeutic drugs for treating cancer. Expand
Pharmacologic Differences Among the SSRIs: Focus on Monoamine Transporters and the HPA Axis
TLDR
Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use, and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Expand
...
1
2
3
4
5
...