Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol

Kimura, Yasuyuki; Maeda, Jun; Yamada, Makiko; Takahata, Keisuke; Yokokawa, Keita; Ikoma, Yoko; Seki, Chie; Ito, Hiroshi; Higuchi, Makoto; Suhara, Tetsuya

doi:10.1007/s00213-016-4464-x

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…We collected data from neuroimaging datasets in our two previous clinical studies ([UMIN000008232] (Kimura et al, 2017 ), [UMIN000007240]), which had been registered in the University Hospital Medical Information Network Clinical Trials Registry. The participants were 34 nonsmoking male volunteers (age, 23 ± 1.9 years; body mass index, 20.9 ± 1.9 kg/m 2 ; mean ± SD ).…”

Section: Methodsmentioning

confidence: 99%

“…3D volumetric acquisition of a T1‐weighted gradient echo sequence produced a gapless series of thin sagittal sections. The scan parameters for our participants were either of the following sets: (1) TE, 9.2 ms; TR, 21 ms; flip angle, 30°; and slice thickness, 1 mm ( n = 17; subjects who completed both [ 11 C]raclopride and [ 18 F]FE‐PE2I PET; UMIN000008232; Kimura et al, 2017 ); or (2) TE, 3.43 ms; TR, 2300 ms; flip angle, 30°; and slice thickness, 1 mm ( n = 17; subjects who completed [ 11 C]raclopride PET only) (UMIN000007240).…”

Section: Methodsmentioning

confidence: 99%

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Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Kurose

Kubota

Takahata

et al. 2021

Human Brain Mapping

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Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for this regulatory process in the human brain and its disruptions in neuropsychiatric disorders. Here, we aimed to investigate associations of striatal dopamine transporter (DAT) and D 2 receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D 2 receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [ 11 C]raclopride and [ 18 F]FE-PE2I, respectively, were acquired along with T1-weighted magnetic resonance imaging data in our previous studies, and were re-analyzed in this work. We quantified the binding potentials (BP ND ) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BP ND and regional GM volume were then examined by voxel-based morphometry. In line with the functional and anatomical connectivity, [ 11 C]raclopride BP ND in the limbic striatum was positively correlated with volumes of the uncal/parahippocampal gyrus and adjacent temporal areas. Similarly, we found positive correlations between the BP ND of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BP ND in the sensorimotor striatum and volumes of the somatosensory and supplementary motor areas. By contrast, no significant correlation was found between [ 18 F]FE-PE2I BP ND and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D 2 receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Kurose

Kubota

Takahata

et al. 2021

Human Brain Mapping

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“…On the other hand, the DAT inhibitory effect by 60 mg of dl-methylephedrine as evaluated by PET and [ 18 F]FE-PE2I did not show a significant difference from the placebo. Also, the degree of inhibition was approximately 4%, much lower than the 25–74% of inhibition by other prohibited drugs ( 24 , 25 , 31 ). It is considered that there is no significant dopamine release at this level of DAT occupancy, because in the mazindol study, even with a single administration of 1.5 mg, DAT occupancy was about 25%, but a decrease of BP ND , which reflects dopamine release, was only about 2.8 to 4.6% ( 25 ).…”

Section: Discussionmentioning

confidence: 72%

“…DAT occupancy of methylphenidate with [ 11 C]cocaine was reported as 40–74% in the striatum at clinical doses of 10–60 mg ( 31 ). As for mazindol, DAT occupancy in the striatum was approximately 25% with 1.5 mg ( 25 ). Compared to those results, DAT occupancy by dl-methylephedrine was quite low, approximately 4% in the present study, and there was no significant difference compared with placebo.…”

Section: Discussionmentioning

confidence: 99%

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Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I

et al. 2022

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RationaleSince ephedrine has a dopamine transporter (DAT) inhibitory effect similar to amphetamine, dl-methylephedrine, a derivative of ephedrine, is considered to have the characteristics of a central nervous system stimulant due to the DAT inhibitory effect. For example, the World Anti-Doping Agency categorizes dl-methylephedrine as a stimulant in the prohibited list for competitions. Assuming to have the same effect as ephedrine, the urinary concentration of dl-methylephedrine is regulated below 10 μg/mL, as is ephedrine. However, the extent to which dl-methylephedrine affects brain function is not yet fully understood.ObjectivesThe purpose of this study was to evaluate DAT occupancy by a single oral administration of a daily dose of dl-methylephedrine using positron emission tomography (PET) with [18F]FE-PE2I to characterize its stimulatory effect on the central nervous system.MethodsNine healthy male volunteers were enrolled in the study. The experiments were designed as a placebo-controlled randomized double-blind crossover comparative study. After the first PET scan in a drug-free state, the second and third PET scans were performed with randomized dosing at 60 mg of dl-methylephedrine or placebo. The plasma and urine concentrations of dl-methylephedrine were measured just before and after the PET scans, respectively.ResultsMean urine and plasma concentrations of dl-methylephedrine were 13.9 μg/mL and 215.2 ng/mL, respectively. Mean DAT occupancy in the caudate was 4.4% for dl-methylephedrine and 1.2% for placebo. Mean DAT occupancy in the putamen was 3.6% for dl-methylephedrine and 0.5% for placebo. There was no significant difference of DAT occupancies between the groups.ConclusionIn this study, the urinary concentration of dl-methylephedrine (13.9 μg/mL) was higher than the prohibited reference value (10.0 μg/mL), and there was no significant difference in DAT occupancy between dl-methylephedrine and placebo. These findings suggest that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose of dl-methylephedrine.

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Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation

Shen

Wang

et al. 2022

The Journal of Nutritional Biochemistry

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Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol

Cited by 7 publications

References 20 publications

Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I

Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation

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Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol

Cited by 7 publications

References 20 publications

Relationship between regional gray matter volumes and dopamine D2 receptor and transporter in living human brains

Relationship between regional gray matter volumes and dopamine D2 receptor and transporter in living human brains

Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I

Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation

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Product

Resources

About

Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains