Characterization of Desamino-5-[125I]Iodo-3-Methoxy-Zacopride ([125I]MIZAC) binding to 5-HT3 receptors in the rat brain

Hewlett, William A.; Fridman, S. M.; Trivedl, Bakula L.; Schmidt, D. E.; Ebert, Michael H.

doi:10.1016/s0278-5846(98)00012-8

Cited by 16 publications

(8 citation statements)

References 26 publications

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“…10 Similar findings have been reported with [ 125 I]MIZAC which exhibited greater binding around the temporal cortex, hippocampus, frontal cortex, and the medulla. 11 Our results on the binding of [ 18 F]fesetron in the hippocampus and cerebellum/brain stem regions (AP and NTS) are consistent with the findings of 5-HT 3 receptors. The structural similarity of these 3-aminoquinuclidinyl derivatives thus appears to manifest in their binding profiles (Figs.…”

supporting

confidence: 89%

“…5 Zacopride is a 3-aminoquinuclidinyl derivative exhibiting antiemetic effects which were found to be greater for its ( S )-isomer. 6–8 In order to study the distribution of these receptors, [ 3 H]zacopride, 9 related radioiodinated derivatives, [ 125 I]DAIZAC 10 and [ 125 I] MIZAC 11 and other compounds without the 3-aminoquinuclidinyl moiety as in [ 3 H]GR65630 12 have been synthesized (Fig. 1).…”

mentioning

confidence: 99%

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Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

Pithia

Liang

Pan

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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Serotonin 5-HT3 receptors are involved in various brain functions including as an emesis target during cancer chemotherapy. We report here the development of (S)-2,3-dimethoxy-5-(3′-[18F]fluoropropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide ([18F]fesetron) as a potential PET imaging agent for serotonin 5-HT3 receptors. By radiolabeling((S)-2,3-dimethoxy-5-(3′-tosyloxypropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide) with fluorine-18, (S)-[18F]fesetron was obtained in 5 to 10% decay-corrected yields and with specific activities >74 GBq/μmol at the end of radiosynthesis. PET imaging in rats showed low uptake of [18F]fesetron in the brain with retention of binding in the striatal and cerebellar regions. Using colliculi as a reference region, ratios were 3.4 for striata and 2.5 for cerebellum. Ex vivo brain PET analysis displayed binding of [18F]fesetron in the hippocampus, striatum and cerebellar regions. Cerebellar regions corresponded to area postrema and nucleus tract solitaris known to contain 5-HT3 receptors. Dorsal hippocampus showed the highest uptake with ratio of >17 with respect to colliculi, while area postrema and striata had ratios of >10. Thus, [18F]fesetron exhibited a unique binding profile to rat brain regions known to contain significant amounts of serotonin 5-HT3 receptors. However, the very low brain uptake limits its usefulness as a PET radiotracer in this animal model.

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confidence: 89%

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confidence: 99%

Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

Pithia

Liang

Pan

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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“…For instance, in humans, 5-HT 3 binding is relatively high in the caudate and putamen and lower in the cortex (Abi-Dargham et al, 1993), whereas the reverse seems to hold true for the rodent brain (Laporte et al, 1992;Hewlett et al, 1998;Morales et al, 1998). These areas are crucially involved in the vomiting reflex and it is likely that the therapeutic effects of 5-HT 3 antagonists in chemotherapy-induced and radiationinduced nausea and vomiting are because of 5-HT 3 receptor blockade within this complex.…”

Section: The 5-ht 3 Receptormentioning

confidence: 99%

Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

Ellenbroek

Prinssen

2015

Behavioural Pharmacology

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In one of his earlier papers, Lex Cools stated that the 'concept of an impaired balance between the in series connected […] dopamine system, […] 5-HT system and […] noradrenaline system offers a single coherent and integrated theory of schizophrenia' (Cools, 1975). Since then, considerable attention has focused on the interaction between dopamine and 5-HT and it is now well accepted that most antipsychotics (especially the second-generation drugs) modulate both dopaminergic and serotonergic receptors. However, the vast majority of research has focused on the 5-HT1A, 5-HT2A and 5-HT2C receptors. In the present paper, we review the literature pertaining to the 5-HT3 receptor, the only ionotropic 5-HT receptor. We discuss both the interactions between 5-HT3 receptors and dopamine, and the animal and human literature investigating the role of 5-HT3 receptors in schizophrenia. The results show that the interactions between 5-HT3 receptors and dopamine are complex, but that 5-HT3 receptors do not have a strong influence on the positive symptoms of schizophrenia. However, when added to standard antipsychotic medication, several recent studies have found that 5-HT3 receptor antagonists can induce a statistically significantly improvement in negative and cognitive symptoms. The implications of these findings in relation to animal modelling and drug development are discussed.

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“…Although substituted benzamides have been evaluated as dopamine receptor agents [13] another class of substituted benzamides such as zacopride has been studied as potential imaging agents for serotonin 5HT3 receptors [20]. Comparison of the structure of norfallypride with zacopride (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of 18F-Norfallypride in the rodent brain using PET imaging

Pithia

Gulati

Pandey

et al. 2013

Nuclear Medicine and Biology

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Characterization of Desamino-5-[125I]Iodo-3-Methoxy-Zacopride ([125I]MIZAC) binding to 5-HT3 receptors in the rat brain

Cited by 16 publications

References 26 publications

Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

Synthesis and biological evaluation of 18F-Norfallypride in the rodent brain using PET imaging

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