An autoradiograph is an image on an X-ray film or nuclear emulsion produced by the pattern of decay emissions from a distribution of a radioactive substance. Alternatively, the autoradiograph is also available as a digital image, due to the recent development of scintillation gas detectors or rare-earth phosphorimaging systems. The film or emulsion is apposed to the labeled tissue section to obtain the autoradiograph. The auto- prefix indicates that the radioactive substance is within the sample, as distinguished from the case of historadiography or microradiography, in which the sample is marked using an external source. Some autoradiographs can be examined microscopically for localization of silver grains in which the process is termed micro-autoradiography. For example, micro-autoradiography was used to examine whether atrazine was being metabolized by the hornwort plant or by epiphytic microorganisms in the biofilm layer surrounding the plant.
Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.
Raclopride is a typical antipsychotic. It acts as a selective antagonist on D2 dopamine receptors. It has been used in trials studying Parkinson Disease.
Translocator protein (TSPO) is an 18 kDa protein mainly found on the outer mitochondrial membrane. It was first described as peripheral benzodiazepine receptor (PBR), a secondary binding site for diazepam, but subsequent research has found the receptor to be expressed throughout the body and brain. In humans, the translocator protein is encoded by the TSPO gene. It belongs to a family of tryptophan-rich sensory proteins. Regarding intramitochondrial cholesterol transport, TSPO has been proposed to interact with StAR to transport cholesterol into mitochondria, though evidence is mixed.
Etifoxine, sold under the trade name Stresam among others, is a nonbenzodiazepine anxiolytic agent, primarily indicated for short-term management of adjustment disorder, specifically instances of situational depression accompanied by anxiety, such as stress-induced anxiety. Administration is by mouth. Side effects associated with etifoxine use include slight drowsiness, headache, skin eruptions, and allergic reactions. In rare cases, etifoxine has been linked to severe skin and liver toxicity, as well as menstrual bleeding between periods. Unlike benzodiazepines, etifoxine does not cause sedation or lack of coordination. Etifoxine acts as a GABAA receptor positive allosteric modulator and as a ligand for translocator proteins. Both mechanisms are conjectured to contribute to its anxiolytic properties.
WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent antagonist at the former receptor. It is closely related to WAY-100135.
Nisoxetine, originally synthesized in the Lilly research laboratories during the early 1970s, is a potent and selective inhibitor for the reuptake of norepinephrine (noradrenaline) into synapses. It currently has no clinical applications in humans, although it was originally researched as an antidepressant. Nisoxetine is now widely used in scientific research as a standard selective norepinephrine reuptake inhibitor. It has been used to research obesity and energy balance, and exerts some local analgesia effects.
Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO. This protein has multiple functions, among which is regulation of steroidogenesis, particularly the production of neuroactive steroids such as allopregnanolone in the brain. In both animal and human trials, emapunil produced fast acting anxiolytic and anti-panic effects, without producing sedation or withdrawal symptoms following cessation of use. Emapunil is also used in its 11C radiolabelled form to map the distribution of TSPO receptors in the brain.
FGIN-1-27 is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO. It is thought to produce anxiolytic effects by stimulating steroidogenesis of neuroactive steroids such as allopregnanolone.
FGIN-1-43 is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO. It is thought to produce anxiolytic effects by stimulating steroidogenesis of neuroactive steroids such as allopregnanolone, and is several times more potent than the related drug FGIN-127.
SSR-180,575 is a drug which acts as a selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO. It has been shown to have neuroprotective and cardioprotective effects and to stimulate steroidogenesis of pregnenolone in the brain, which may be linked to its neuroprotective action.
DAA-1097 is a drug which acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO, but with no affinity at central benzodiazepine receptors. It has anxiolytic effects in animal studies.
DAA-1106 is a drug which acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO, but with no affinity at the GABAA receptor. It has anxiolytic effects in animal studies. DAA-1106 has a sub-nanomolar binding affinity (Ki) of 0.28 nM, and has been used extensively in its 3H or 11C radiolabelled form to map TSPO in the body and brain, which has proved especially helpful in monitoring the progress of neurodegenerative diseases such as Alzheimer's disease.
Ro5-4864 (4'-chlorodiazepam) is a drug which is a benzodiazepine derivative of diazepam. However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for GABAA receptors and lacks typical benzodiazepine effects, instead being sedative yet also convulsant and anxiogenic in effects. Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor", later renamed to mitochondrial translocator protein 18kDa (TSPO). Despite its convulsant effects, at lower doses Ro5-4864 has proved to be neuroprotective and has become widely used for research into the role of the TSPO protein in neurotoxicity. In vitro studies and rodent models also suggest the possibility of analgesic, antidepressant, cardioprotective, and anti-cancer effects.
Brain positron emission tomography is a form of positron emission tomography (PET) that is used to measure brain metabolism and the distribution of exogenous radiolabeled chemical agents throughout the brain. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data from brain PET are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.
Tryptophan-rich sensory proteins (TspO) are a family of proteins that are involved in transmembrane signalling. In either prokaryotes or mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway. They are associated with the major outer membrane porins and with the voltage-dependent anion channel.
DPA-714 or N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide is a selective ligand for the translocator protein (TSPO) currently under evaluation for several clinical applications. For this reason, a practical, multigram synthetic route for its preparation has been described.
DPA-713 or N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide is a selective ligand for the translocator protein (TSPO).
Vassilios Papadopoulos, DPharm, PhD, DSc (hon), born February 18, 1961, in Athens, Greece, is a scholar, researcher, inventor, professor, and university administrator who has served as dean of the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences at the University of Southern California in Los Angeles, California, since 2016. Previously, he was the associate vice president and director of the Biomedical Graduate Research Organization at Georgetown University from 2005 to 2007, and the executive director and chief scientific officer of the Research Institute of the McGill University Health Center from 2007 to 2015.
Julie C. Price is an American medical physicist and professor of radiology at Massachusetts General Hospital (MGH), Harvard Medical School (HMS), as well as the director of PET Pharmacokinetic Modeling at the Athinoula A. Martinos Center at MGH. Price is a leader in the study and application of quantitative positron emission tomography (PET) methods. Prior to this, Price worked with Pittsburgh colleagues to lead the first fully quantitative pharmacokinetic evaluations of 11C-labeled Pittsburgh compound-B (PIB), one of the most widely used PET ligands for imaging amyloid beta plaques. As a principal investigator at MGH, Price continues work to validate novel PET methods for imaging biological markers of health and disease in studies of aging and neurodegeneration, including studies of glucose metabolism, protein expression, neurotransmitter system function, and tau and amyloid beta plaque burden.
