5-I-R91150

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5-I-R91150
5-I-R91150 Structure.svg
Identifiers
  • 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C23H29FIN3O2
Molar mass 525.407 g·mol−1
3D model (JSmol)
  • Ic1cc(c(OC)cc1N)C(=O)NC3(CCN(CCCc2ccc(F)cc2)CC3)C
  • InChI=1S/C23H29FIN3O2/c1-23(27-22(29)18-14-19(25)20(26)15-21(18)30-2)9-12-28(13-10-23)11-3-4-16-5-7-17(24)8-6-16/h5-8,14-15H,3-4,9-13,26H2,1-2H3,(H,27,29) Yes check.svgY
  • Key:MIPHZURHMMOGLS-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

5-I-R91150 (or R93274) is a compound that acts as a potent and selective antagonist of 5-HT2A receptors. [1] Its main application is as its iodine-123 radiolabeled form, in which it can be used in SPECT scanning [2] in human neuroimaging studies, to examine the distribution of the 5-HT2A receptor subtype in the brain, e.g. with respect to sex and age [3] and in adults with Asperger syndrome [4] or Alzheimer's disease. [5]

An alternative 5-HT2A receptor ligand also used in neuroimaging is altanserin.

Related Research Articles

<span class="mw-page-title-main">Positron emission tomography</span> Medical imaging technique

Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body.

<span class="mw-page-title-main">Single-photon emission computed tomography</span> Nuclear medicine tomographic imaging technique

Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera, but is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.

A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide. By virtue of its radioactive decay, it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products. Radiolabeling or radiotracing is thus the radioactive form of isotopic labeling. In biological contexts, experiments that use radioisotope tracers are sometimes called radioisotope feeding experiments.

A radioligand is a microscopic particle which consists of a therapeutic radioactive isotope and the cell-targeting compound - the ligand. The ligand is the target binding site, it may be on the surface of the targeted cancer cell for therapeutic purposes. Radioisotopes can occur naturally or be synthesized and produced in a cyclotron/nuclear reactor. The different types of radioisotopes include Y-90, H-3, C-11, Lu-177, Ac-225, Ra-223, In-111, I-131, I-125, etc. Thus, radioligands must be produced in special nuclear reactors for the radioisotope to remain stable. Radioligands can be used to analyze/characterize receptors, to perform binding assays, to help in diagnostic imaging, and to provide targeted cancer therapy. Radiation is a novel method of treating cancer and is effective in short distances along with being unique/personalizable and causing minimal harm to normal surrounding cells. Furthermore, radioligand binding can provide information about receptor-ligand interactions in vitro and in vivo. Choosing the right radioligand for the desired application is important. The radioligand must be radiochemically pure, stable, and demonstrate a high degree of selectivity, and high affinity for their target.

<span class="mw-page-title-main">Neuroimaging</span> Set of techniques to measure and visualize aspects of the nervous system

Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Increasingly it is also being used for quantitative research studies of brain disease and psychiatric illness. Neuroimaging is highly multidisciplinary involving neuroscience, computer science, psychology and statistics, and is not a medical specialty. Neuroimaging is sometimes confused with neuroradiology.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.

Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellurium-123 emits gamma radiation with a predominant energy of 159 keV. In medical applications, the radiation is detected by a gamma camera. The isotope is typically applied as iodide-123, the anionic form.

<span class="mw-page-title-main">RTI-55</span> Chemical compound

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<span class="mw-page-title-main">RTI-121</span> Chemical compound

(–)-2β-Carboisopropoxy-3β-(4-iodophenyl)tropane is a stimulant drug used in scientific research, which was developed in the early 1990s. RTI-121 is a phenyltropane based, highly selective dopamine reuptake inhibitor and is derived from methylecgonidine. RTI-121 is a potent and long-lasting stimulant, producing stimulant effects for more than 10 hours after a single dose in mice which would limit its potential uses in humans, as it might have significant abuse potential if used outside a medical setting. However RTI-121 occupies the dopamine transporter more slowly than cocaine, and so might have lower abuse potential than cocaine itself.

Ioflupane (<sup>123</sup>I) Chemical compound

Ioflupane (123I) is the international nonproprietary name (INN) of a cocaine analogue which is a neuro-imaging radiopharmaceutical drug, used in nuclear medicine for the diagnosis of Parkinson's disease and the differential diagnosis of Parkinson's disease over other disorders presenting similar symptoms. During the DaT scan procedure it is injected into a patient and viewed with a gamma camera in order to acquire SPECT images of the brain with particular respect to the striatum, a subcortical region of the basal ganglia. The drug is sold under the brand name Datscan and is manufactured by GE Healthcare, formerly Amersham plc.

<span class="mw-page-title-main">Altanserin</span> Chemical compound

Altanserin is a compound that binds to the 5-HT2A receptor. Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography (PET) studies of the brain, i.e., studies of the 5-HT2A neuroreceptors. Besides human neuroimaging studies altanserin has also been used in the study of rats.

<span class="mw-page-title-main">DASB</span> Chemical compound

DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the serotonin transporter. Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography (PET) since around year 2000. In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain, since it has high selectivity for the serotonin transporter.

Gated SPECT is a nuclear medicine imaging technique, typically for the heart in myocardial perfusion imagery. An electrocardiogram (ECG) guides the image acquisition, and the resulting set of single-photon emission computed tomography (SPECT) images shows the heart as it contracts over the interval from one R wave to the next. Gated myocardial perfusion imaging has been shown to have high prognostic value and sensitivity for critical stenosis.

<span class="mw-page-title-main">Setoperone</span> Chemical compound

Setoperone is a compound that is a ligand to the 5-HT2A receptor. It can be radiolabeled with the radioisotope fluorine-18 and used as a radioligand with positron emission tomography (PET). Several research studies have used the radiolabeled setoperone in neuroimaging for the studying neuropsychiatric disorders, such as depression or schizophrenia.

Iofetamine (<sup>123</sup>I) Pair of enantiomers

Iofetamine, brand names Perfusamine, SPECTamine), or N-isopropyl-(123I)-p-iodoamphetamine (IMP), is a lipid-soluble amine and radiopharmaceutical drug used in cerebral blood perfusion imaging with single-photon emission computed tomography (SPECT). Labeled with the radioactive isotope iodine-123, it is approved for use in the United States as a diagnostic aid in determining the localization of and in the evaluation of non-lacunar stroke and complex partial seizures, as well as in the early diagnosis of Alzheimer's disease.

Iomazenil Chemical compound

Iomazenil is an antagonist and partial inverse agonist of benzodiazepine and a potential treatment for alcohol use disorder. The compound was introduced in 1989 by pharmaceutical company Hoffmann-La Roche as an Iodine-123-labelled SPECT tracer for imaging benzodiazepine receptors in the brain. Iomazenil is an analogue of flumazenil (Ro15-1788).

<span class="mw-page-title-main">25CN-NBOH</span> Chemical compound

25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.

<span class="mw-page-title-main">Nifene</span> Chemical compound

Nifene is a high affinity, selective nicotinic α4β2* receptor partial agonist used in medical research for nicotinic acetylcholine receptors, usually in the form of nifene (18F) as a positron emission tomography (PET) radiotracer.

Preclinical or small-animal Single Photon Emission Computed Tomography (SPECT) is a radionuclide based molecular imaging modality for small laboratory animals. Although SPECT is a well-established imaging technique that is already for decades in use for clinical application, the limited resolution of clinical SPECT (~10 mm) stimulated the development of dedicated small animal SPECT systems with sub-mm resolution. Unlike in clinics, preclinical SPECT outperforms preclinical coincidence PET in terms of resolution and, at the same time, allows to perform fast dynamic imaging of animals.

Theranostics, also known as theragnostics, is a technique commonly used in personalised medicine. For example in nuclear medicine, one radioactive drug is used to identify (diagnose) and a second radioactive drug is used to treat (therapy) cancerous tumors. In other words, theranostics combines radionuclide imaging and radiation therapy which targets specific biological pathways.

References

  1. Peremans K, Audenaert K, Coopman F, Jacobs F, Dumont F, Slegers G, et al. (2003). "Regional binding index of the radiolabeled selective 5-HT2A antagonist 123I-5-I-R91150 in the normal canine brain imaged with single photon emission computed tomography". Veterinary Radiology & Ultrasound. 44 (3): 344–51. doi: 10.1111/j.1740-8261.2003.tb00467.x . PMID   12816380.
  2. Busatto GF, Pilowsky LS, Costa DC, Mertens J, Terriere D, Ell PJ, et al. (February 1997). "Initial evaluation of 123I-5-I-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects". European Journal of Nuclear Medicine. 24 (2): 119–24. doi:10.1007/BF02439542. PMID   9021107. S2CID   33466680.
  3. Baeken C, D'haenen H, Flamen P, Mertens J, Terriere D, Chavatte K, et al. (December 1998). "123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects". European Journal of Nuclear Medicine. 25 (12): 1617–22. doi:10.1007/s002590050339. PMID   9871092. S2CID   29644617.
  4. Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S, et al. (May 2006). "Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study". The American Journal of Psychiatry. 163 (5): 934–6. doi:10.1176/appi.ajp.163.5.934. PMID   16648340.
  5. Versijpt J, Van Laere KJ, Dumont F, Decoo D, Vandecapelle M, Santens P, et al. (2003). "Imaging of the 5-HT2A system: age-, gender-, and Alzheimer's disease-related findings". Neurobiology of Aging. 24 (4): 553–61. doi:10.1016/S0197-4580(02)00137-9. PMID   12714112. S2CID   44937787.

Further reading