"of substance abuse. The most common chemical substance which is abused by pop musicians is cocaine, because of its neurological effects. Stimulants like cocaine increase alertness and cause feelings of euphoria, and can therefore make the performer feel as though they in some ways ‘own the stage’. One way in which substance abuse is harmful for a performer (musicians especially) is if the substance being abused is aspirated. The lungs are an important organ used by singers, and addiction to cigarettes may seriously harm the quality of their performance. Smoking causes harm to alveoli, which are responsible for absorbing oxygen."
"7-Nitroindazole 7-Nitroindazole, or 7-NI, is a heterocyclic small molecule containing an indazole ring that has been nitrated at the 7 position. Nitroindazole acts as a selective inhibitor for neuronal nitric oxide synthase, a hemoprotein enzyme that, in neuronal tissue, converts arginine to citrulline and nitric oxide (NO). Nitric oxide can diffuse through the plasma membrane into neighbouring cells, allowing cell signalling, so nitroindazole indirectly inhibits this signalling process. Other inhibitors exist such as 3-bromo-7-nitroindazole, which is more potent but less specific, or NPA (N-propyl-L-arginine), which acts on a different site. 7-Nitroindazole is under investigation as a possible protective agent against"
"Nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase, an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter. Poisoning by a nerve agent leads to constriction of pupils, profuse salivation, convulsions, and involuntary urination and defecation, with the first symptoms appearing in seconds after exposure. Death by asphyxiation or cardiac arrest may follow in minutes due to the loss of the body's control over respiratory and other muscles. Some nerve agents are readily"
"are exceptions — the venom of the black-necked spitting cobra (""Naja nigricollis""), an elapid, consists mainly of cytotoxins, while that of the Mojave rattlesnake (""Crotalus scutulatus""), a viperid, is primarily neurotoxic. There are numerous other types of toxin which both elapids and viperids may carry. ""The beginning of a new impulse"": A) An exchange of ions (charged atoms) across the nerve cell membrane sends a depolarizing current towards the end of the nerve cell (cell terminus). B) When the depolarizing current arrives at the nerve cell terminus, the neurotransmitter acetylcholine (ACh), which is held in vesicles, is released into the"
"nerve damage caused by excitotoxicity or neurodegenerative diseases. It may act by reducing oxidative stress or by decreasing the amount of peroxynitrite formed in these tissues. These effects are related to the inhibition of type 1 nitric oxide synthase. However, anticonvulsive effect is derived from some other mechanisms. 7-Nitroindazole 7-Nitroindazole, or 7-NI, is a heterocyclic small molecule containing an indazole ring that has been nitrated at the 7 position. Nitroindazole acts as a selective inhibitor for neuronal nitric oxide synthase, a hemoprotein enzyme that, in neuronal tissue, converts arginine to citrulline and nitric oxide (NO). Nitric oxide can diffuse through"
"bond between it and the intermediate and forms two products. So inhibitors usually contain a nonhydrolyzable hydroxyethylene or hydroxyethylamine groups that mimic the tetrahedral intermediate. Since they share a similar structure and electrostatic arrangement to the transition state of substrates they can still fit into the active site but cannot be broken down. So hydrolysis cannot occur. Strychnine is a neurotoxin that causes death by affecting nerves that control muscular contraction and cause respirational difficulty. The impulse is transmitted between the synapse through a neurotransmitter called acetylcholinesterase. it is released into the synapse between nerve cells and bind to receptors"
"decreasing its breakdown, or enhancing its effect on neurons. The nerve impulse is characterised by a great influx of sodium ions through channels in the neuron's cell membrane followed by an efflux of potassium ions through other channels. The neuron is unable to fire again for a short time (known as the refractory period), which is mediated by another potassium channel. The flow through these ion channels is governed by a ""gate"" which is opened by either a voltage change or a chemical messenger known as a ligand (such as a neurotransmitter). These channels are another target for anticonvulsant drugs."
"5,7-Dihydroxytryptamine 5,7-Dihydroxytryptamine (5,7-DHT) is a purported neurotoxin used in scientific research to decrease concentrations of serotonin in the brain. The mechanism behind this effect isn't well understood, but many believe (without clear substantiation) that it selectively kills serotonergic neurons, in a similar way that 6-hydroxydopamine (6-OHDA) is used to kill dopaminergic cells. What is known is that this compound is in fact not selective in depleting serotonin content, but also depletes norepinephrine. To selectively deplete serotonin stores, it is commonly administered in conjunction with desmethylimipramine (desipramine)[3], which inhibits the norepinephrine transporter. 3. Martin-Iverson, M.T., Leclere, J.F. and Fibiger, H.C., Cholinergic-dopaminergic"
"known as 4-amino-tetrahydrobiopterin (4-ABH), an analogue of BH (a cofactor of NOS), is an NOS inhibitor that is under development as a neuroprotective agent for the treatment of traumatic brain injury. Other NOS inhibitors that have been or are being researched for possible clinical use include cindunistat, A-84643, ONO-1714, L-NOARG, NCX-456, VAS-2381, GW-273629, NXN-462, CKD-712, KD-7040, and guanidinoethyldisulfide, among others. Nitric oxide synthase Nitric oxide synthases () (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis,"
"tissues from damage due to low blood supply. Also a neurotransmitter, nitric oxide acts in the nitrergic neurons active on smooth muscle, abundant in the gastrointestinal tract and erectile tissue. Sildenafil (Viagra) works to inhibit the enzyme phosphodiesterase PDE5, which increase the cGMP concentration by inhibiting the conversion to GMP. Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Humans with atherosclerosis, diabetes, or hypertension often show impaired NO pathways. Nitric oxide (NO) is a mediator of vasodilation in blood vessels. It is induced by several"
"by neurotransmitters, though there are also electrical pathways between some neurons. Neurotransmitters can inhibit impulse firing (primarily done by γ-aminobutyric acid, or GABA) or they can excite the neuron into firing (primarily done by glutamate). A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron. When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis,"
"tadalafil (Cialis), which elevate cGMP concentration by inhibiting its degradation by PDE5. A role for NO in various common psychiatric disorders including schizophrenia, bipolar disorder and major depressive disorder has been proposed and supported by several clinical findings. These findings may also implicate the potential of drugs that alter NO signalling such as SNP in their treatment. Such a role is also supported by the findings of the recent SNP clinical trial. Nitroprusside is an inorganic compound with the formula Na[Fe(CN)NO], usually encountered as the dihydrate, Na[Fe(CN)NO]·2HO. This red-colored sodium salt dissolves in water or ethanol to give solutions containing"
"Charybdotoxin Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion ""Leiurus quinquestriatus hebraeus"" (""deathstalker"") that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from ""Leiurus quinquestriatus hebraeus"". The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin, derived from the venom of scorpion Pandinus imperator. Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins. Charybdotoxin, a 37 amino acid, 4 kDa neurotoxin"
"anabaseine. GTS-21 GTS-21 (DMBX-A) is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent. Both GTS-21 itself and its demethylated active metabolite 4-OH-GTS-21 display nootropic and neuroprotective effects, and GTS-21 is being investigated for the treatment of Alzheimer's disease, nicotine dependence, and, most significantly, for schizophrenia. The laboratory name GTS-21 means that it is the 21st chemical compound created by Gainesville (University of Florida in Gainesville) and Tokushima (Taiho Pharmaceutical) Scientists. DMXB-A –"
"GTS-21 GTS-21 (DMBX-A) is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent. Both GTS-21 itself and its demethylated active metabolite 4-OH-GTS-21 display nootropic and neuroprotective effects, and GTS-21 is being investigated for the treatment of Alzheimer's disease, nicotine dependence, and, most significantly, for schizophrenia. The laboratory name GTS-21 means that it is the 21st chemical compound created by Gainesville (University of Florida in Gainesville) and Tokushima (Taiho Pharmaceutical) Scientists. DMXB-A – 3-2,4-dimethoxybenzylidene"
"251D is still unknown. PTX 251D has several effects. It rapidly induces convulsions and death to mice and insects (LD50 being, respectively, 10 mg/kg and 150 ng/larvae). These convulsions are the result of the uncontrollable distortion of the sodium-potassium equilibrium in the neurons. This is caused by the inhibition of the VGSCs. It also acts as cardiac depressor, causing cardiac arrest. This can be explained by its negative effect on the cardiac VGSC hNav1.5/β1. Although nothing is known of how well PTX 251D penetrates into the brain where convulsions are originated, the observation of convulsions can be explained through inhibition"
"as ALS, Parkinson's disease, and convulsive disorders like epilepsy. Honokiol disrupts the interfaces post synaptic density protein (PSD95) and neuronal nitric oxide synthase (nNOS). PSD95 and nNOS coupling to the NMDA receptor causes a conformational change responsible for the intracellular influx of Ca which could in turn be a pathway for neurotoxicity. Calcium overloading can also cause damage by over-activation of calcium-stimulated enzymes. Honokiol can reduce calcium influx through inhibition of the fMLP, AlF, and thapsigargin G-protein pathways. Honokiol has been shown to inhibit hepatitis C virus (HCV) infection in vitro. It has weak in vitro activity against human immunodeficiency"
"this area. Botulinum toxin (aka botulinum neurotoxin, BoNT, and sold under the trade name Botox) inhibits the release of acetylcholine at the neuromuscular junction by interfering with SNARE proteins. This toxin crosses into the nerve terminal through the process of endocytosis and subsequently interferes with SNARE proteins, which are necessary for ACh release. By doing so, it induces a transient flaccid paralysis and chemical denervation localized to the striated muscle that it has affected. The inhibition of the ACh release does not set in until approximately two weeks after the injection is made. Three months after the inhibition occurs, neuronal"
"parts per billion (ppb) concentrations. The following nerve agents have been identified with this multiwavelength LPAS: Other gases and air contaminants identified with LPAS include: Non-dispersive infrared techniques have been reported to be used for gaseous nerve agent detection. Traditional IR absorption has been reported to detect gaseous nerve agents. Fourier transform infrared (FTIR) spectroscopy has been reported to detect gaseous nerve agents. Nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase, an enzyme"
"trauma. BNN-27 BNN-27, also known as 17α,20""R""-epoxypregn-5-ene-3β,21-diol, is a synthetic neurosteroid and ""microneurotrophin"" and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA and p75, receptors for nerve growth factor (NGF) and other neurotrophins, as well as for DHEA and DHEA sulfate (DHEA-S). BNN-27 has neuroprotective and neurogenic effects and has been suggested as a potential novel treatment for neurodegenerative diseases and brain trauma. In 2011, the surprising discovery was made that DHEA, as well as DHEA-S, directly bind to and activate the TrkA and p75 with high affinity. DHEA"
"BNC-210 BNC210 (also known as IW-2143 during its time licensed to Ironwood Pharmaceuticals) is an anxiolytic drug that acts via negative allosteric modulation of the α-nicotinic acetylcholine receptor, by Bionomics Limited. It is currently being investigated for the treatment of post traumatic stress disorder. The drug has demonstrated clinically significant anxiety reduction in both animal models and in Phase I trials. It appears to be devoid of significant sedation or memory-impairing side effects, as well as lacking addictive potential in rat discriminatory models. Phase I trials have shown no serious side effects. Bionomics previously licensed it to Ironwood Pharmaceuticals in"
"hallucinations. A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be involved in the etiology of Alzheimer's disease. Targeting the glutamatergic system, specifically NMDA receptors, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system. Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. By binding to the NMDA receptor with a higher affinity than Mg ions, memantine is able to inhibit the prolonged influx of Ca ions, particularly from extrasynaptic receptors, which forms the basis of neuronal excitotoxicity. The low affinity, uncompetitive nature, and rapid"
"(17α-hydroxylase/17,20 lyase) inhibitors, such as abiraterone acetate, may mainly block production of excitatory neurosteroids. Antigonadotropins may also have the effect of lowering circulating neurosteroid levels. The translocator protein (TSPO), also initially described as the peripheral benzodiazepine receptor (PBR), is a mitochondrial protein that is involved in neurosteroid biosynthesis. It is activated by certain benzodiazepines such as diazepam and midazolam, and via this action, inhibitory neurosteroid levels are increased. Selective TSPO activators, such as emapunil, are under investigation for clinical use as possible anxiolytics. Progesterone, which is the endogenous precursor to the inhibitory neurosteroids 5α-dihydroprogesterone and allopregnanolone, as well as, more"
"Vagusstoff Vagusstoff (literally translated from German as ""Vagus Substance"") refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate. Discovered in 1921 by physiologist Otto Loewi, ""vagusstoff"" was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered. It was later confirmed to be acetylcholine, which was first identified by Sir Henry Hallett Dale in 1914. Because of his pioneering experiments, in 1936 Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Dale. By the time Loewi began his experiments there was much"
"BNN-27 BNN-27, also known as 17α,20""R""-epoxypregn-5-ene-3β,21-diol, is a synthetic neurosteroid and ""microneurotrophin"" and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA and p75, receptors for nerve growth factor (NGF) and other neurotrophins, as well as for DHEA and DHEA sulfate (DHEA-S). BNN-27 has neuroprotective and neurogenic effects and has been suggested as a potential novel treatment for neurodegenerative diseases and brain trauma. In 2011, the surprising discovery was made that DHEA, as well as DHEA-S, directly bind to and activate the TrkA and p75 with high affinity. DHEA was"
"synaptic function, and often are restricted to synapses that use a specific neurotransmitter. For example, curare is a poison that stops acetylcholine from depolarizing the postsynaptic membrane, causing paralysis. Strychnine blocks the inhibitory effects of the neurotransmitter glycine, which causes the body to pick up and react to weaker and previously ignored stimuli, resulting in uncontrollable muscle spasms. Morphine acts on synapses that use endorphin neurotransmitters, and alcohol increases the inhibitory effects of the neurotransmitter GABA. LSD interferes with synapses that use the neurotransmitter serotonin. Cocaine blocks reuptake of dopamine and therefore increases its effects. During the 1950s, Bernard Katz"
"effect of gas dissolving into nerve membranes and causing temporary disruption in nerve transmissions. While the effect was first observed with air, other gases including argon, krypton and hydrogen cause very similar effects at higher than atmospheric pressure. Some of these effects may be due to antagonism at NMDA receptors and potentiation of GABA receptors, similar to the mechanism of nonpolar anesthetics such diethyl ether or ethylene. However, their reproduction by the very chemically inactive gas argon makes them unlikely to be a strictly chemical bonding to receptors in the usual sense of a chemical bond. An indirect physical effect"
"synthesis article). Strychnine is a neurotoxin which acts as an antagonist of glycine and acetylcholine receptors. It primarily affects the motor nerve fibers in the spinal cord which control muscle contraction. An impulse is triggered at one end of a nerve cell by the binding of neurotransmitters to the receptors. In the presence of an inhibitory neurotransmitter, such as glycine, a greater quantity of excitatory neurotransmitters must bind to receptors before there will be an action potential generated. Glycine acts primarily as an agonist of the glycine receptor, which is a ligand-gated chloride channel in neurons located in the spinal"
"Oxidopamine Oxidopamine, also known as 6-hydroxydopamine (6-OHDA) or 2,4,5-trihydroxyphenethylamine, is a neurotoxic synthetic organic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. 6-OHDA is thought to enter the neurons via the dopamine and noradrenaline (norepinephrine) reuptake transporters. Oxidopamine is often used in conjunction with a selective noradrenaline reuptake inhibitor (such as desipramine) to selectively destroy dopaminergic neurons. The main use for oxidopamine in scientific research is to induce Parkinsonism in laboratory animals such as mice, rats and monkeys, in order to develop and test new medicines and treatments for Parkinson's disease. In order to"
"in the postsynaptic cell. Then an action potential is generated and transmitted through the postsynaptic cell to start a new cycle. Glycine can inhibit the activity of neurotransmitter receptor, thus a larger amount of acetylcholinesterase is required to trigger an action potential. This makes sure that the generation of nervous impulse is under tight control. However, this control is broken down when strychnine is added. It inhibits glycine receptors(a chloride channel) and a much lower level of neurotransmitter concentration can trigger an action potential. Nerves now constantly transmit signals and cause excessive muscular contraction, leading to asphyxiation and death. Diisopropyl"
"Norketamine Norketamine, or ""N""-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist (K = 1.7 µM and 13 µM for (""S"")-(+)-norketamine and (""R"")-(–)-norketamine, respectively), but is about 3–5 times less potent as an anesthetic in comparison. Also, similarly again to ketamine, norketamine binds to the μ- and κ-opioid receptors. Relative to ketamine, norketamine is much more potent as an antagonist of the α-nicotinic acetylcholine receptor, and produces rapid antidepressant effects in animal models which have been reported to correlate with its activity at this"
"a primate model, PCP was found to induce cognitive impairments which were reversed with clozapine. Serotonin is a monoamine neurotransmitter which has been associated with schizophrenia. The psychedelic drug classes indoleamines and phenethylamines can affect serotoninergic 5-HT receptors. LSD, an indoleamine, affects startle habituation and prepulse inhibition of startle, which are indicators of human schizophrenia. γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter. The GABAergic system may be involved in schizophrenia due to its interactions with the dopaminergic system. Picrotoxin, an antagonist for the GABA receptor, produces prepulse inhibition of startle in rats. Haloperidol, an antipsychotic drug, reduces this effect."
"central nervous system is the sulfated octapeptide, CCK-8S. In both humans and rodents, studies clearly indicate that elevated CCK levels causes increased anxiety. The site of the anxiety-inducing effects of CCK seems to be central with specific targets being the basolateral amygdala, hippocampus, hypothalamus, peraqueductal grey, and cortical regions. The CCK tetrapeptide fragment CCK-4 (Trp-Met-Asp-Phe-NH) reliably causes anxiety and panic attacks (panicogenic effect) when administered to humans and is commonly used in scientific research for this purpose of in order to test new anxiolytic drugs. Positron emission tomography visualization of regional cerebral blood flow in patients undergoing CCK-4 induced panic"