Synthesis and evaluation of 5-HT3 receptor antagonist [11C]KF17643

Ishiwata, Kiichi; Saito, Noriko; Yanagawa, Koji; Furuta, Riko; Ishii, Shin‐ichi; Kiyosawa, Motohiro; Homma, Yoshio; Suzuki, Fumio; Senda, Michio

doi:10.1016/0969-8051(95)02079-9

Cited by 15 publications

(20 citation statements)

References 28 publications

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“…Ishiwata et al radiolabelled several specific 5‐HT 3 receptor antagonists: Y‐25130 (azasetron): N ‐(1‐azabicyclo[2.2.2]oct‐3‐yl)‐6‐chloro‐4‐methyl‐3‐oxo‐3,4‐dihydro‐2 H ‐1,4‐benzoxazine‐8‐carboxamide), YM060: ( R )‐5‐[1‐methyl‐3‐indolyl)carbonyl]‐4,5,6,7‐tetrahydro‐1 H ‐benzimidazole, and KF17643: endo ‐8‐methyl‐8‐azabicyclo[3.2.1]oct‐3‐yl 2‐( n ‐propyloxy)‐4‐quinolinecarboxylate for PET imaging. [ 11 C]Y‐25130 and [ 11 C]YM060 brain uptake in mice was low for both compounds, possibly due to low lipophilicity of [ 11 C]Y‐25130, or ionization of the tertiary amine or both.…”

Section: Current Radioligands For Imaging the 5‐ht Systemmentioning

confidence: 99%

5‐HT radioligands for human brain imaging with PET and SPECT

Paterson

Kornum

Nutt

et al. 2011

Medicinal Research Reviews

145

129

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The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging.

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Section: Current Radioligands For Imaging the 5‐ht Systemmentioning

confidence: 99%

5‐HT radioligands for human brain imaging with PET and SPECT

Paterson

Kornum

Nutt

et al. 2011

Medicinal Research Reviews

145

129

View full text Add to dashboard Cite

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“…It would be important to establish if 5‐HT 3 and/or 5‐HT 4 receptors are responsible for the action(s) of drugs used in the treatment of IBS symptoms. These evaluations became feasible with the development of imaging tracers specific for these sites 57,58 . The data described here suggest a need for imaging studies to obtain a better understanding of the pathophysiology of IBS.…”

Section: Discussionmentioning

confidence: 89%

The effects of the 5‐HT₃ antagonist, alosetron, on brain serotonin synthesis in patients with irritable bowel syndrome

Nakai

Dikšić

Kumakura

et al. 2005

Neurogastroenterology Motil

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Serotonin (5-HT) plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Using alpha-[(11)C]methyl-L-tryptophan-positron emission tomography (PET), it was demonstrated that brain 5-HT synthesis is increased in patients with IBS, in a gender-specific manner. The aims of the study were to evaluate the effects of alosetron on brain 5-HT synthesis in patients with IBS. Six male and five female non-constipation-predominant IBS patients were enrolled. The subjects received alosetron or a placebo for 14 days, separated by a 2-week washout period. On day 14, rectal distensions commenced just prior to the PET scan (which was performed for 80 min), and continued for 20-min periods. The functional images were analysed with SPM99. Alosetron vs placebo treatments, in a randomized, double-blinded, crossover manner, were studied. 5-HT synthesis was greater in several regions in the males than in the females during the alosetron treatment, whereas there was no region in which the females had greater synthesis. There were significant gender-treatment interactions of synthesis in the cingulate gyrus, caudate nucleus, globus pallidus, and cerebellum. The gender differences in the effect of alosetron on brain 5-HT synthesis may be related to the gender differences in the efficacy of alosetron.

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“…A closely related analogue of MDL72222 was radiolabeled by Ishiwata et al for PET imaging: [ 11 C]KF17643 . Nevertheless, [ 11 C]KF17643 displayed nonspecific binding [ 171 ].…”

Section: 5-ht 3 Receptorsmentioning

confidence: 99%