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18-methoxycoronaridine
18-Methoxycoronaridine (18-MC, or MM-110) is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemists Upul K. Bandarage and Martin E. Kuehne from the University of Vermont. In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose. It has also been shown to produce anorectic effects in obese rats, most likely due to the same actions on the reward system which underlie its anti-addictive effects against drug addiction. 18-MC was in the early stages of human testing by the California-based drug development company Savant HWP before being acquired by MindMed, a Canadian pharmaceutical company newly listed on the NASDAQ in April 2021.
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Methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. ''Methamphetamine'' properly refers to a specific chemical substance, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms. It is rarely prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy such as Adderall and Vyvanse. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine. Both racemic methamphetamine and dextromethamphetamine are illicitly trafficked ...
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Ganglion Type Nicotinic Receptor
The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor,Pharmacology, (Rang, Dale, Ritter & Moore, , 5th ed., Churchill Livingstone 2003) p. 138. is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability. As with other nicotinic acetylcholine receptors, the α3β4 receptor is pentameric α3)m(β4)n where m + n = 5 The exact subunit stoichiometry is not known and it is possible that more than one functional α3β4 receptor assembles in vivo with varying subunit stoichiometries. Ligands which inhibit the α3β4 receptor have been shown to modulate drug-seeking behavior, making α3β4 a promising target for the development of novel antiaddictive agents. Ligands Agonists * Acetylcholine (endogenous neurotransmitter that binds non-s ...
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Ibogaine
Ibogaine is a naturally occurring psychoactive substance found in plants in the family Apocynaceae such as '' Tabernanthe iboga'', '' Voacanga africana'', and '' Tabernaemontana undulata''. It is a psychedelic with dissociative properties. Preliminary research indicates that it may help counter drug addiction. Its use has been associated with serious side effects and death. Between the years 1990 and 2008, a total of 19 fatalities temporally associated with the ingestion of ibogaine were reported, from which six subjects died of acute heart failure or cardiopulmonary arrest. The total number of subjects who have used it without major side effects during this period remains unknown. It is used as an alternative medicine treatment for drug addiction in some countries. Its prohibition in other countries has slowed scientific research. Ibogaine is also used to facilitate psychological introspection and spiritual exploration. Various derivatives of ibogaine designed to lack psychede ...
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Opioid Withdrawal
Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, nausea, vomiting, diarrhea, sweating, and an increased heart rate. Opioid use triggers a rapid adaptation in cellular signalling pathways that means, when rapidly withdrawn, there can be adverse physiological effects. All opioids, both recreational drugs and medications, when reduced or stopped, can lead to opioid withdrawal symptoms. When withdrawal symptoms are due to recreational opioid use, the term opioid use disorder is used, whereas when due to prescribed medications, the term ''prescription opioid use disorder'' is used. Opioid withdrawal can be helped by the use of opioid replacement therapy, and symptoms may be relieved by the use of medications including lofexidine and clonidine. Signs and symptoms Withdrawal from any opi ...
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Basolateral Amygdala
The basolateral amygdala, or basolateral complex, consists of the lateral, basal and accessory-basal nuclei of the amygdala. The lateral nuclei receives the majority of sensory information, which arrives directly from the temporal lobe structures, including the hippocampus and primary auditory cortex. The basolateral amygdala also receives dense neuromodulatory inputs from ventral tegmental area (VTA), locus coeruleus (LC), and basal forebrain, whose integrity are important for associative learning. The information is then processed by the basolateral complex and is sent as output to the central nucleus of the amygdala. This is how most emotional arousal is formed in mammals. Function The amygdala has several different nuclei and internal pathways; the basolateral complex (or basolateral amygdala), the central nucleus, and the cortical nucleus are the most well-known. Each of these has a unique function and purpose within the amygdala. Fear response The basolateral amygdala ...
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Tegmentum
The tegmentum (from Latin for "covering") is a general area within the brainstem. The tegmentum is the ventral part of the midbrain and the tectum is the dorsal part of the midbrain. It is located between the ventricular system and distinctive basal or ventral structures at each level. It forms the floor of the midbrain ( mesencephalon) whereas the tectum forms the ceiling. It is a multisynaptic network of neurons that is involved in many subconscious homeostatic and reflexive pathways. It is a motor center that relays inhibitory signals to the thalamus and basal nuclei preventing unwanted body movement. The tegmentum area includes various different structures, such as the rostral end of the reticular formation, several nuclei controlling eye movements, the periaqueductal gray matter, the red nucleus, the substantia nigra, and the ventral tegmental area. The tegmentum is the location of several cranial nerve (CN) nuclei. The nuclei of CN III and IV are located in the tegmentum p ...
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Interpeduncular Nucleus
The interpeduncular nucleus (IPN) is an unpaired, ovoid cell group at the base of the midbrain tegmentum. It is located in the mesencephalon below the interpeduncular fossa. As the name suggests, the interpeduncular nucleus lies ''in between'' the cerebral peduncles. Composition The Interpeduncular nucleus is primarily GABAergic and contains at least two neuron clusters of different morphologies. The region is divided into 7 paired and unpaired subnuclei Subdivisions The presence of non-homologous subdivisions of the Interpeduncular nucleus was first noticed by Cajal over a hundred years ago. The currently recognized standard subdivision notation was mostly established by Hammill and Lenn in 1984 by combining the work and notations of four groups. Although most of their proposed convention stuck, at some point the proposed "rostral lateral" sub-nucleus was renamed "dorsomedial" and became immortalized in brain atlases. * Apical sub-nucleus (IPA) Unpaired sub-nucleus. Former nam ...
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Medial Habenula
In neuroanatomy, habenula (diminutive of Latin ''habena'' meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well-conserved structures in all vertebrate animals. Currently, this term refers to this separate cell mass in the caudal portion of the dorsal diencephalon, known as the epithalamus, found in all vertebrates on both sides of the third ventricle. It connects the forebrain and midbrain within the epithalamus. It is embedded in the posterior end of the stria medullaris from which it receives most of its afferent fibers. By way of the fasciculus retroflexus (habenulointerpeduncular tract) it projects to the interpeduncular nucleus and other paramedian cell groups of the midbrain tegmentum. Although they were predominantly studied for the ...
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Kappa Opioid Receptor
Kappa (uppercase Κ, lowercase κ or cursive ; el, κάππα, ''káppa'') is the 10th letter of the Greek alphabet, representing the voiceless velar plosive sound in Ancient and Modern Greek. In the system of Greek numerals, has a value of 20. It was derived from the Phoenician letter kaph . Letters that arose from kappa include the Roman K and Cyrillic К. The uppercase form is identical to the Latin K. Greek proper names and placenames containing kappa are often written in English with "c" due to the Romans' transliterations into the Latin alphabet: Constantinople, Corinth, Crete. All formal modern romanizations of Greek now use the letter "k", however. The cursive form is generally a simple font variant of lower-case kappa, but it is encoded separately in Unicode for occasions where it is used as a separate symbol in math and science. In mathematics, the kappa curve is named after this letter; the tangents of this curve were first calculated by Isaac Barrow in ...
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Sigma Receptor
Sigma receptors (σ-receptors) are protein cell surface receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 receptors (σ1) and sigma-2 receptors (σ2), which are classified as sigma receptors for their pharmacological similarities, even though they are evolutionarily unrelated. The fungal protein ERG2, a C-8 sterol isomerase, falls into the same protein family as sigma-1. Both localize to the ER membrane, although sigma-1 is also reported to be a cell surface receptor. Sigma-2 is an EXPREA domain protein (citation needed) with a mostly intracellular (ER membrane) localization. Classification Because the σ-receptor was originally discovered to be agonized by benzomorphan opioids and antagonized by naltrexone, σ-receptors were originally believed to be a type of opioid receptor. When the σ1 receptor was isolated and cloned, it was ...
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Sodium Channel
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change ("voltage-gated", "voltage-sensitive", or "voltage-dependent" sodium channel; also called "VGSCs" or "Nav channel") or a binding of a substance (a ligand) to the channel ( ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through three different states called resting, active and inactive states. Even though the resting and inactive states would not allow the ions to flow through the channels the difference exists with respect to their structural conformation. Selectivity Sodium channels are highly selective for the transport of ions across cell m ...
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