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CI-966
CI-966 (developmental code name) is a central nervous system depressant acting as a GABA reuptake inhibitor, specifically a highly potent and selective blocker of the GABA transporter 1 (GAT-1) ( IC50 = 0.26 μM), and hence indirect and non-selective GABA receptor full agonist. It was investigated as a potential anticonvulsant, anxiolytic, and neuroprotective therapeutic but was discontinued during clinical development due to the incidence of severe adverse effects at higher doses and hence was never marketed. In a phase I human clinical trial while under development for the treatment of epilepsy, CI-966 was assessed at doses of 1–10 mg, 25 mg, and 50 mg. While the 1–10 mg dosages were well tolerated, the 25 mg dose produced memory deficits and the 50 mg dose was found to produce "a variety of severe neurological and psychiatric symptoms" and "serious psychotic adverse effects" of prolonged (several-day) duration and demonstrated "severe adverse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABA Reuptake Inhibitor
A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission. Indications GRIs may be used in the clinical treatment of seizures, convulsions, or epilepsy as anticonvulsants/antiepileptics, anxiety disorders such as generalized anxiety disorder (GAD), social phobia (SP) also known as social anxiety disorder (SAD), and panic disorder (PD) as anxiolytics, insomnia as hypnotics, muscle tremors or spasms as muscle relaxants, and chronic pain as analgesics. They may also potentially be used as anesthetics in surgery. Effects GRIs can induce a wide range of psychological and physiological effects, including: * general and subjective alteration in consciousness * dizziness * blurry vision * diplopia or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muscimol
Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of ''Amanita muscaria'' and related species of mushroom. Muscimol is a potent and selective orthosteric agonist for the GABAA receptors and displays sedative-hypnotic, depressant and hallucinogenic psychoactivity. This colorless or white solid is classified as an isoxazole. Muscimol went under clinical trial phase I for epilepsy, but the trial was discontinued. Biochemistry Muscimol is one of the psychoactive compounds responsible for the effects of ''Amanita muscaria'' intoxication. Ibotenic acid, a neurotoxic secondary metabolite of ''Amanita muscaria'', serves as a prodrug to muscimol when the mushroom is ingested or dried, converting to muscimol via decarboxylation. Muscimol is produced in the mushrooms ''Amanita muscaria'' (fly agaric) and ''Amanita pantherina'', along with muscarine (which is present in trace amounts and it is not active), muscazone, and ibotenic acid. ''A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Memory Deficit
Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use of various sedatives and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that was caused. There are two main types of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is the inability to retrieve information that was acquired before a particular date, usually the date of an accident or operation. In some cases the memory loss can extend back decades, while in others the person may lose only a few months of memory. Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can occur simul ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABAA Receptor
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−). Depending on the membrane potential and the ionic concentration difference, this can result in ionic fluxes across the pore. If the membrane potential is higher than the equilibrium potential (also known as the reversal potential) for chloride ions, when the receptor is activated Cl− will flow into the cell. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring at the postsynaptic cell. The reversal potential of the GABAA-mediated inhibitory postsynaptic potential (IPSP) in normal solution is −70 mV, contrasting the GABAB IPSP (-100 mV). T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hallucinogen
Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants. However, certain hallucinogens such as Fly agaric as well as other gabaergic hallucinogenics are more often considered to technically be hypnotics, therefore indicating another separate subcategory of drugs which can substantially alter visual perception. Etymology The word ''hallucinogen'' is derived from the word ''hallucination''. The term ''hallucinate'' dates back to around 1595–1605, and is derived from the Latin ''hallūcinātus'', the past participle of ''(h)allūcināri'', meaning "to wander in the mind." Characteristics Leo Hollister gave five criteria for classifying a drug as hallucinogenic.Glennon RA. Classical drugs: an introductory overview. In Lin GC and Gle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mania
Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together with lability of affect." During a manic episode, an individual will experience rapidly changing emotions and moods, highly influenced by surrounding stimuli. Although mania is often conceived as a "mirror image" to depression, the heightened mood can be either euphoric or dysphoric. As the mania intensifies, irritability can be more pronounced and result in anxiety or anger. The symptoms of mania include elevated mood (either euphoric or irritable), flight of ideas and pressure of speech, increased energy, decreased need and desire for sleep, and hyperactivity. They are most plainly evident in fully developed hypomanic states. However, in full-blown mania, they undergo progressively severe exacerbations and become more and more obscured by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NMDA Receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA receptor, AMPA and kainate receptors. Depending on its subunit composition, its Ligand (biochemistry), ligands are glutamate and glycine (or D-Serine, D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Magnesium, Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a “coincidence detector” and only once both of these conditions are met, the channel opens and it allows cation, positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions. The NMDA receptor is ionotropic, meaning it is a pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABA-ergic neurons. Its molecular formula is . Glutamic acid exists in three optically isomeric forms; the dextrorotatory -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971. Its molecular structure could be idealized as HOOC−CH()−()2−COOH, with two carboxyl groups −COOH and one amino group −. However, in the solid state and mildly acidic water solu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book ''The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as cad ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdrawal, decreased emotional expression, and apathy. Symptoms typically develop gradually, begin during young adulthood, and in many cases never become resolved. There is no objective diagnostic test; diagnosis is based on observed behavior, a history that includes the person's reported experiences, and reports of others familiar with the person. To be diagnosed with schizophrenia, symptoms and functional impairment need to be present for six months (DSM-5) or one month (ICD-11). Many people with schizophrenia have other mental disorders, especially substance use disorders, depressive disorders, anxiety disorders, and obsessive–compulsive disorder. About 0.3% to 0.7% of people are diagnosed with schizophrenia during their lifetime. In 2 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Psychotomimetic
A drug with psychotomimetic (also known as psychotogenic) actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administration of such a drug. Some rarely used drugs of the opioid class have psychotomimetic effects. Particularly, mixed kappa receptor agonist mu receptor antagonist opioid analgesics can cause dose-related psychotomimesis. This adverse effect, incidence 1–2%, limits their use. Pentazocine and butorphanol fall under this opioid class. There is evidence that cannabinoids are psychotomimetic, especially delta-9-tetrahydrocannabinol (Δ9-THC). D'Souza et al. (2004) found that intravenous THC produced effects that resemble schizophrenia in both the positive symptoms (hallucinations, delusions, paranoia, and disorganized thinking) and negative symptoms (avolition, asociality, apathy, alogia, and anhedonia). Certain strains of cannabis may be mor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
