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.
Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.
Nuclear medicine, is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, radiology done inside out, because it records radiation emitted from within the body rather than radiation that is transmitted through the body from external sources like X-ray generators. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a physiological imaging modality. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.
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.
The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes the positive symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.
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 13.2232 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.
RTI(-4229)-55, also called RTI-55 or iometopane, is a phenyltropane-based psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991. RTI-55 is a non-selective dopamine reuptake inhibitor derived from methylecgonidine. However, more selective analogs are derived by conversion to "pyrrolidinoamido" RTI-229, for instance. Due to the large bulbous nature of the weakly electron withdrawing iodo halogen atom, RTI-55 is the most strongly serotonergic of the simple para-substituted troparil based analogs. In rodents RTI-55 actually caused death at a dosage of 100 mg/kg, whereas RTI-51 and RTI-31 did not. Another notable observation is the strong propensity of RTI-55 to cause locomotor activity enhancements, although in an earlier study, RTI-51 was actually even stronger than RTI-55 in shifting baseline LMA. This observation serves to highlight the disparities that can arise between studies.
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon H. Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.
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.
DaT Scan commonly refers to a diagnostic method, based on SPECT imaging, to investigate if there is a loss of dopaminergic neurons in striatum. The term may also refer to a brand name of Ioflupane (123I) tracer used for the study. The scan principle is based on use of the radiopharmaceutical Ioflupane (123I) which binds to dopamine transporters (DaT). The signal from them is then detected by the use of single-photon emission computed tomography (SPECT) which uses special gamma-cameras to create a pictographic representation of the distribution of dopamine transporters in the brain.
Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors. It is taken by mouth. The most prevalent side effects include nausea, mild sedation, fatigue, and dizziness. At higher dosages, there is an increased risk for restlessness, insomnia, and tremors.
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 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).
Dopamine supersensitivity psychosis is a hypothesis that attempts to explain the phenomenon in which psychosis (e.g., hallucinations, delusions) occurs despite treatment with escalating doses of antipsychotics. Dopamine supersensitivity may be caused by the dopamine receptor D2 antagonizing effect of antipsychotics, causing a compensatory increase in D2 receptors within the brain that sensitizes neurons to endogenous release of the neurotransmitter dopamine. Because psychosis is thought to be mediated—at least in part—by the activity of dopamine at D2 receptors, the activity of dopamine in the presence of supersensitivity may paradoxically give rise to worsening psychotic symptoms despite antipsychotic treatment at a given dose. This phenomenon may co-occur with tardive dyskinesia, a rare movement disorder that may also be due to dopamine supersensitivity.
Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).
