Building Bridges In Neuropharmacology: New therapeutic approaches for psychiatric and neurodegenerative disorders

Bailey, Alexis; Berwick, Daniel C.; Camarini, Rosana; Scavone, Cristóforo

doi:10.1111/bph.15711

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…After that, a freshly eluted pertechnetate solution (~ 350 MBq) from a Moly generator was added to this mixture and subsequently incubated at room temperature for 25 min. In order to determine the optimal labeling conditions, different combinations of factors affecting the labeling yield were studied using varying amounts of fonturacetam hydrazide (5-50 µg), Stannous chloride dihydrate (25-250 µg) at different pH values (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) for different reaction times (5-40 min).…”

Section: Labeling Of Fonturacetam Hydrazidementioning

confidence: 99%

“…The human brain is a complex organ. The detailed molecular and subcellular processes and neuronal cell interactions underlying central nervous system diseases such as psychiatric conditions and neurodegenerative disorders are poorly understood [1,2]. Single-photon emission computed tomography (SPECT) has grown in importance as a clinical diagnostic and research modality over the last few decades [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Radiolabeling and evaluation of fonturacetam hydrazide as a radiotracer for visualization of brain function

El-Kawy

Shweeta

Sallam

2023

J Radioanal Nucl Chem

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Abstract[99mTc] fonturacetam hydrazide was radiosynthesized to assess neuropsychiatric disorders by targeting the brain. The nootropic drug was labeled with technetium-99m, and factors affecting the labeling yield were studied. At optimum conditions, the radiocomplex was obtained at a high radiochemical yield (98.9%) and was stable in saline for up to 36 h and serum for more than 24 h. Labeled fonturacetam hydrazide was characterized and assessed in silico. Biodistribution studies in mice showed that the brain uptake of the complex was 8.8% injected dose per gram (% ID/g) at 5 min post-injection, surpassing the commercially available [99mTc] ECD (4.7% ID/g) and [99mTc] HMPAO (2.25% ID/g). All results suggested that the tracer is a good candidate to image the human brain for assessing neuropsychiatric disorders.

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Section: Labeling Of Fonturacetam Hydrazidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radiolabeling and evaluation of fonturacetam hydrazide as a radiotracer for visualization of brain function

El-Kawy

Shweeta

Sallam

2023

J Radioanal Nucl Chem

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Quantifying AMPARs with 99mTc-omberacetam: a novel diagnostic radiotracer for ischemic stroke

Azhari,

Hashem

2023

J.Umm Al-Qura Univ. Appll. Sci.

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Synaptic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is thought to cause excitotoxicity brain ischemia. However, given the current inability to quantify AMPARs density in live human brains, clinical translation has been limited. In this study, in vivo and in vitro experiments were conducted to evaluate the factors affecting omberacetam drug labeling with technetium-99m as a potential radiotracer of AMPARs in brain imaging. Healthy Swiss albino mice (adult male; n = 25; weight 25–30 g; age 10–14 weeks) underwent Shimadzu modeling, followed by a random intravenous injection of 99mTc-omberacetam (0.2 mL, 3.7 MBq), which was subsequently radiosynthesized in the brain-targeting AMPARs utilizing a single-photon emission computed tomography nuclear neuroimaging. Under optimal conditions, 99mTc-omberacetam with a highest radiochemical purity of 98.9% was obtained with an optimum binding (energy = − 82.3 kcal/mol) to brain AMPARs and was stable in human serum for > 24 h. A high brain uptake was noted within a time window of 15–60 min. At 5 min, this signal uptake was 8.9 ± 0.1% of the injected dose per gram (ID/g), crossing the blood–brain barrier and surpassing the uptake of commercially available brain perfusion imaging agents such as 125I-iododomperidone (5.6% ID/g at 5 min) in mice, 99mTc-HMPAO (2.25% ID/g at 2 min) in rats, and 99mTc-ECD (4.7% ID/g at 6 h) in humans. This study is the first to show the feasibility of 99mTc-omberacetam radiotracing for human brain imaging. This could be a novel diagnostic and therapeutic neuroprotective target for the hyperacute stage of ischemic stroke. Graphical abstract

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µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

Nisbett,

Vendruscolo,

Koob

2024

Transl Psychiatry

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Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential μ−opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective μ−opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ−opioid receptor antagonist, norbinaltorphimine, we demonstrate that μ−opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ−opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.

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Building Bridges In Neuropharmacology: New therapeutic approaches for psychiatric and neurodegenerative disorders

Cited by 3 publications

References 12 publications

Radiolabeling and evaluation of fonturacetam hydrazide as a radiotracer for visualization of brain function

Radiolabeling and evaluation of fonturacetam hydrazide as a radiotracer for visualization of brain function

Quantifying AMPARs with 99mTc-omberacetam: a novel diagnostic radiotracer for ischemic stroke

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

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