Cocaine is a tropane alkaloid that acts as a central nervous system (CNS) stimulant. As an extract, it is mainly used recreationally, and often illegally for its euphoric and rewarding effects. It is also used in medicine by Indigenous South Americans for various purposes and rarely, but more formally, as a local anaesthetic by medical practitioners in more developed countries. It is primarily obtained from the leaves of two Coca species native to South America: Erythroxylum coca and E. novogranatense. After extraction from the plant, and further processing into cocaine hydrochloride, the drug is administered by being either snorted, applied topically to the mouth, or dissolved and injected into a vein. It can also then be turned into free base form, in which it can be heated until sublimated and then the vapours can be inhaled.
Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from the algae Digenea simplex. They have been traditionally classified as a non-NMDA-type receptor, along with the AMPA receptor. KARs are less understood than AMPA and NMDA receptors, the other ionotropic glutamate receptors. Postsynaptic kainate receptors are involved in excitatory neurotransmission. Presynaptic kainate receptors have been implicated in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism.
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.
Vanoxerine is a piperazine derivative which is a potent and selective dopamine reuptake inhibitor (DRI). Vanoxerine binds to the target site on the dopamine transporter (DAT) ~ 50 times more strongly than cocaine, but simultaneously inhibits the release of dopamine. This combined effect only slightly elevates dopamine levels, giving vanoxerine only mild stimulant effects. Vanoxerine has also been observed to be a potent blocker of the IKr (hERG) channel. Vanoxerine also binds with nanomolar affinity to the serotonin transporter.
Fenobam is an imidazole derivative developed by McNeil Laboratories in the late 1970s as a novel anxiolytic drug with an at-the-time-unidentified molecular target in the brain. Subsequently, it was determined that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5, and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists.
Naphthylaminopropane (PAL-287) is an experimental drug under investigation as of 2007 for the treatment of alcohol and stimulant addiction.
Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of cocaine and/or crack despite substantial harm and adverse consequences. The Diagnostic and Statistical Manual of Mental Disorders, classifies problematic cocaine use as a "Stimulant use disorder". The International Classification of Diseases, includes "Cocaine dependence" as a classification (diagnosis) under "Disorders due to use of cocaine".
Metabotropic glutamate receptor 5 is an excitatory Gq-coupled G protein-coupled receptor predominantly expressed on the postsynaptic sites of neurons. In humans, it is encoded by the GRM5 gene.
Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene.
Tezampanel is a drug originally developed by Eli Lilly which acts as a competitive antagonist of the AMPA and kainate subtypes of the ionotropic glutamate receptor family, with selectivity for the GluR5 subtype of the kainate receptor. It has neuroprotective and anticonvulsant properties, the former of which may, at least in part, occur via blockade of calcium uptake into neurons.
2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. After being originally patented as a liquid crystal for LCDs, it was developed by the pharmaceutical company Novartis in the late 1990s. It was found to produce neuroprotective effects following acute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant and anxiolytic effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.
3-( ethynyl)pyridine (MTEP) is a research drug that was developed by Merck & Co. as a selective allosteric antagonist of the metabotropic glutamate receptor subtype mGluR5. Identified through structure-activity relationship studies on an older mGluR5 antagonist MPEP, MTEP has subsequently itself acted as a lead compound for newer and even more improved drugs.
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
SIB-1757 is a drug used in scientific research which was one of the first compounds developed that acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It has anti-hyperalgesia effects in animals. SIB-1757 along with other mGluR5 antagonists has been shown to have neuroprotective and hepatoprotective effects, and it is also used to study the role of the mGluR5 receptor in brain development.
CDPPB is a drug used in scientific research which acts as a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5. It has antipsychotic effects in animal models, and mGluR5 modulators are under investigation as potential drugs for the treatment of schizophrenia, as well as other applications.
Substance use disorder (SUD) is the persistent use of drugs despite substantial harm and adverse consequences as a result of their use. The National Institute of Mental Health (NIMH) states that "Substance use disorder (SUD) is a treatable mental disorder that affects a person's brain and behavior, leading to their inability to control their use of substances like legal or illegal drugs, alcohol, or medications. Symptoms can be moderate to severe, with addiction being the most severe form of SUD". Substance use disorders (SUD) are considered to be a serious mental illness that fluctuates with the age that symptoms first start appearing in an individual, the time during which it exists and the type of substance that is used. It is not uncommon for those who have SUD to also have other mental health disorders. Substance use disorders are characterized by an array of mental/emotional, physical, and behavioral problems such as chronic guilt; an inability to reduce or stop consuming the substance(s) despite repeated attempts; operating vehicles while intoxicated; and physiological withdrawal symptoms. Drug classes that are commonly involved in SUD include: alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants, tobacco
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behaviour that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in addiction's development. Classic signs of addiction include compulsive engagement in rewarding stimuli, preoccupation with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification, coupled with delayed deleterious effects.
Mavoglurant (developmental code name AFQ-056) is an experimental drug candidate for the treatment of fragile X syndrome and other conditions which has been discontinued. It exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGluR5).
Camilla Bellone is an Italian neuroscientist and assistant professor in the Department of Basic Neuroscience at the University of Geneva, in Switzerland. Bellone's laboratory explores the molecular mechanisms and neural circuits underlying social behavior and probes how defects at the molecular and circuit level give rise to psychiatric disease states such as Autism Spectrum Disorders.
AZD 9272 is a drug which acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It was unsuccessful in human trials as an analgesic, but continues to be widely used in research especially as its radiolabelled forms.
