Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient

Berding, Georg; Schneider, Udo; Gielow, P.; Buchert, Ralph; Donnerstag, Frank; Brandau, Wolfgang; Knapp, Wolfram H.; Emrich, H. M.; Müller‐Vahl, Kirsten

doi:10.1016/j.pscychresns.2006.02.002

Cited by 21 publications

(16 citation statements)

References 30 publications

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“…Initial attempts by several groups to image CB1 in animal brains examined the feasibility of specific labeling of CB1 in vivo. [18][19][20][21][22][23][24][25][26][27][28] Unfortunately, all of the radioligands initially studied (more than 10; mostly analogues of Δ 9 -tetrahydrocannabinol, the principal psychoactive component of marijuana, cannabinoid agonist WIN 55212-2 and 1) exhibited insufficient properties for quantification of CB1 receptor by PET (low specific binding, high non-specific binding and/or low brain uptake). The attempts to quantify CB1 in the living human brain by SPECT and PET demonstrated low binding potential (BP=0.21 and 0.37) for the radioligands [ 123 I]2 [27] and [ 124 I]2 [28], correspondingly (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…High lipophilicity and tight association to proteins were likely causes of high non-specific binding that resulted in low contrast of the in vivo images with labeled 2. [27,28] Compound [ 11 C]3 (Fig 1) synthesized by our group in the past [21,29] also displayed a low BP (0.6) and relatively low brain uptake in the Rhesus monkey brain due to its high lipophilicity and moderate binding affinity. [29,30] Recently we reported development of JHU75528 4 (Fig 2, Table 1), an analog of Rimonabant having a combination of greater CB1 in vitro binding affinity and lower lipophilicity than those of the previously studied CB1 in vivo radioligands.…”

Section: Introductionmentioning

confidence: 99%

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Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): Development of ligands with optimized lipophilicity and binding affinity

Fan

Kotsikorou

Hoffman

et al. 2009

European Journal of Medicinal Chemistry

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Cyano analogs of Rimonabant with high binding affinity for the cerebral cannabinoid receptor (CB1) and with optimized lipophilicity have been synthesized as potential positron emission tomography (PET) ligands. The best ligands of the series are optimal targets for the future radiolabeling with PET isotopes and in vivo evaluation as radioligands with enhanced properties for PET imaging of CB1 receptors in human subjects. Extracellular electrophysiological recordings in rodent brain slices demonstrated that JHU75528, 4, the lead compound of the new series, has functional CB antagonist properties that are consistent with its structural relationship to Rimonabant. Molecular modeling analysis revealed an important role of the binding of the cyano group with the CB1 binding pocket.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): Development of ligands with optimized lipophilicity and binding affinity

Fan

Kotsikorou

Hoffman

et al. 2009

European Journal of Medicinal Chemistry

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“…Moreover, post mortem studies carried out on patients with schizophrenia have demonstrated that they displayed a greater concentration of CB1 in the cortex of the left frontal cincture (64% above controls) (Zavitsanou, Garrick & Huang, 2004). Berding et al (2006), using the Positron Emission Tomography technique (PET) and the radioligand 124 I-AM281, showed that patients with schizophrenia contain a larger amount of CB1 in various regions of the brain, on the right-hand side, in the base nuclei, where the putamen and globus pallidus were the structures with the most CB1 (Berding et al, 2006). The orbitofrontal cortex, the frontal cincture and the temporal cortex also displayed a sizable expression of CB1.…”

Section: Endocannabinoids and Mental Healthmentioning

confidence: 99%

An integrative overview of the cannabinergic system and mental health

Garcı́a

Rueda-Orozco

Belmont

et al. 2017

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Background. The endocannabinoid system (eCBs) is one of the modulatory systems widely expressed in the brain. It consists of receptors expressed in the cytoplasmic (CB1 and CB2), the mitochondrial membrane (CB1), and the endogenous ligands known as endocannabinoids, such as anandamide, 2AG and oleamide. CB1 has been found in excitatory and inhibitory neurons in the pre- and post-synaptic membranes. It is expressed in several brain areas such as the hippocampus, dorsal, and ventral striatum, amygdala and prefrontal cortex. The eCBs has been involved in the regulation of learning and memory, mood, energy balance, sleep, and drug addiction. Objective. Integrate existing information about the eCBs and its role in brain function and mental health. Method. Review of the information of basic and clinical relevance obtained from indexed scientific journals (PubMed/Medline, Scopus). Results. Basic and clinical research on eCBs related to central nervous system function is described. Discussion and conclusion. At present, the study of eCBs is of importance. The development of drugs that affect this system may be clinically useful to control different debilitating diseases. This is an area of interest to the scientific community and health care providers.

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“…Among the first candidate SPECT/PET radioligands targeted to cannabinoid receptors, [ 123 (Fig. 4) have enabled quantification of CB1 receptor distribution and occupancy, biokinetic study of drug and drug candidate distribution, and mapping of pathological tissue changes at the basis of human behavioral and brain disorders [48,[73][74][75].…”

Section: The Cb1 Receptor: a Target For Anti-obesity Pharmacotherapymentioning

confidence: 99%

Pharmacotherapeutic targeting of the endocannabinoid signaling system: Drugs for obesity and the metabolic syndrome

Vemuri

Janero

Makriyannis

2008

Physiology & Behavior

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Endogenous signaling lipids ("endocannabinoids") functionally related to Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana (Cannabis), are important biomediators and metabolic regulators critical to mammalian (patho)physiology. The growing family of endocannabinoids, along with endocannabinoid biosynthetic and inactivating enzymes, transporters, and at least two membrane-bound, G-protein coupled receptors, comprise collectively the mammalian endocannabinoid signaling system. The ubiquitous and diverse regulatory actions of the endocannabinoid system in health and disease have supported the regulatory approval of natural products and synthetic agents as drugs that alter endocannabinoid-system activity. More recent data support the concept that the endocananbinoid system may be modulated for therapeutic gain at discrete pharmacological targets with safety and efficacy. Potential medications based on the endocannabinoid system have thus become a central focus of contemporary translational research for varied indications with important unmet medical needs. One such indication, obesity, is a global pandemic whose etiology has a pathogenic component of endocannabinoid-system hyperactivity and for which current pharmacological treatment is severely limited. Application of high-affinity, selective CB1 cannabinoid receptor ligands to attenuate endocannabinoid signaling represents a state-of-the-art approach for improving obesity pharmacotherapy. To this intent, several selective CB1 receptor antagonists with varied chemical structures are currently in advanced preclinical or clinical trials, and one (rimonabant) has been approved as a weight-management drug in some markets. Emerging preclinical data suggest that CB1 receptor neutral antagonists may represent breakthrough medications superior to antagonists/inverse agonists such as rimonabant for therapeutic attenuation of CB1 receptor transmission. Since obesity is a predisposing condition for the cluster of cardiovascular and metabolic derangements collectively known as the metabolic syndrome, effective endocannabinoid-modulatory anti-obesity therapeutics would also help redress other major health problems including type-2 diabetes, atherothrombosis, inflammation, and immune disorders. Pressing worldwide healthcare needs and increasing appreciation of endocannabinoid biology make the rational design and refinement of targeted CB1 receptor modulators a promising route to future medications with significant therapeutic impact against overweight, obesity, obesity-related cardiometabolic dysregulation, and, more generally, maladies having a reward-supported appetitive component.

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Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient

Cited by 21 publications

References 30 publications

Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): Development of ligands with optimized lipophilicity and binding affinity

Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CB1): Development of ligands with optimized lipophilicity and binding affinity

An integrative overview of the cannabinergic system and mental health

Pharmacotherapeutic targeting of the endocannabinoid signaling system: Drugs for obesity and the metabolic syndrome

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