|
GABAA Receptor Negative Allosteric Modulator
A GABAA receptor negative allosteric modulator is a negative allosteric modulator (NAM), or inhibitor, of the GABAA receptor, a ligand-gated ion channel of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). They are closely related and similar to GABAA receptor antagonists. The effects of GABAA receptor NAMs are functionally the opposite of those of GABAA receptor positive allosteric modulators (PAMs) like the benzodiazepines, barbiturates, and ethanol (alcohol). Non-selective GABAA receptor NAMs can produce a variety of effects including convulsions, neurotoxicity, and anxiety, among others. Selective NAMs (or "inverse agonists") of α5 subunit-containing GABAA receptors, such as basmisanil and α5IA, do not have convulsant or anxiogenic effects but instead show cognitive- and memory-enhancing or nootropic-like effects. They are under investigation for the treatment of cognitive impairment in conditions like Down syndrome and schizophrenia. In addition, th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Negative Allosteric Modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that an allosteric modulator binds to (i.e., an ''allosteric site'') is not the same one to which an endogenous agonist of the receptor would bind (i.e., an ''orthosteric site''). Modulators and agonists can both be called receptor ligands. Allosteric modulators can be 1 of 3 types either: positive, negative or neutral. Positive types increase the response of the receptor by increasing the probability that an agonist will bind to a receptor (i.e. affinity), increasing its ability to activate the receptor (i.e. efficacy), or both. Negative types decrease the agonist affinity and/or efficacy. Neutral types don't affect agonist activity but can stop other modulators from binding to an allosteric site. Some modulators also work as allosteric agonist ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABRA5
Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the ''GABRA5'' gene. Function GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. Subunit selective ligands Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ketamine
Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) and R- (arketamine) two enantiomers and has antidepressant action likely involving additional mechanisms than NMDA antagonism. At anesthetic doses, ketamine induces a state of dissociative anesthesia, a trance-like state providing pain relief, sedation, and amnesia. Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation. As an anesthetic, it is used especially in trauma, Emergency medical services, emergency, and Pediatrics, pediatric cases. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Ketamine is legally used in medicine but is also tightly controlled due to ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NMDA Receptor Antagonist
NMDA receptor antagonists are a class of drugs that work to receptor antagonist, antagonize, or inhibit the action of, the NMDA, ''N''-Methyl-D-aspartate receptor (NMDA receptor, NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they induce is referred to as dissociative anesthesia. Several synthetic opioids function additionally as NMDAR-antagonists, such as pethidine, levorphanol, methadone, dextropropoxyphene, tramadol, and ketobemidone. Some NMDA receptor antagonists, such as ketamine, dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), and nitrous oxide (N2O), are sometimes used as recreational drugs, for their dissociative, hallucinogenic, and euphoriant properties. When used recreationally, they are classified as dissociative drugs. Uses and effects NMDA receptor antagonists induce a state called dissociative drug, dissociative anesthesia, marked by catalepsy, amnesia, and analgesia. Ketamine is a favored anesthet ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rapid-acting Antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal thinking and behavior when taken by children, adolescents, and young adults. Discontinuation syndrome, which resembles recurrent depression in the case of the SSRI class, may occur after stopping the intake of any antidepressant. Research regarding the effectiveness of antidepressants for depression in adults is controversial and has found both benefits and drawbacks. Meanwhile, evidence of benefit in children and adolescents is unclear, even though antidepressant use has considerably increased in children and adolescents in the 2000s. While a 2018 study found that the 21 most commonly prescribed antidepressant medications were slightly more effective than plac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MRK-016
MRK-016 is a selective α5 subunit-containing GABAA negative allosteric modulator, that has nootropic properties. It has been found to produce rapid, ketamine-like antidepressant effects in animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...s of depression. See also * GABAA receptor negative allosteric modulator * GABAA receptor § Ligands References Experimental antidepressants GABAA receptor negative allosteric modulators Isoxazoles Nootropics Triazoles Tert-butyl compounds {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
L-655,708
L-655,708 (FG-8094) is a nootropic drug invented in 1996 by a team working for Merck, Sharp and Dohme, that was the first compound developed which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It acts as an inverse agonist at the α1, α2, α3 and α5 subtypes, but with much higher affinity for α5, and unlike newer α5 inverse agonists such as α5IA, L-655,708 exerts its subtype selectivity purely via higher binding affinity for this receptor subtype, with its efficacy as an inverse agonist being around the same at all the subtypes it binds to. A radiolabelled form of L-655,708 was used to map the distribution of the GABAA α5 subtype in the brain, and it was found to be expressed predominantly in the hippocampus, an area of the brain involved with learning and memory. Activation of this subtype is thought to be largely responsible for producing the cognitive side effects displayed by many benzodia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, flat or inappropriate affect. Symptoms Prodrome, develop gradually and typically begin during young adulthood and rarely resolve. There is no objective diagnostic test; diagnosis is based on observed behavior, a psychiatric history that includes the person's reported experiences, and reports of others familiar with the person. For a diagnosis of schizophrenia, the described symptoms need to have been present for at least six months (according to the DSM-5) or one month (according to the ICD-11). Many people with schizophrenia have other mental disorders, especially mood disorder, mood, anxiety disorder, anxiety, and substance use disorders, substance use disorders, as well as obsessive–compulsive disorder (OCD). About 0.3% to 0.7% of peo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cognitive Impairment
Cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to the cognition process or different areas of cognition. Cognition, also known as cognitive function, refers to the mental processes of how a person gains knowledge, uses existing knowledge, and understands things that are happening around them using their thoughts and senses. Cognitive impairment can be in different domains or aspects of a person's cognitive function including memory, attention span, planning, reasoning, decision-making, language (comprehension, writing, speech), executive functioning, and visuospatial functioning. The term cognitive impairment covers many different diseases and conditions and may also be symptom or manifestation of a different underlying condition. Examples include impairments in overall intelligence (as with intellectual disabilities), specific and restricted impairments in cognitive abilities (such as in learning disorders like dyslexia), neurops ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nootropic
Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self-control. In the United States, nootropics can be over-the-counter drugs and commonly advertised with unproven claims of effectiveness for improving cognition. The Federal Trade Commission and FDA have warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements. Nootropics include both prescription drugs and dietary supplements marketed to enhance brain function, but while FDA-approved drugs have proven benefits and oversight, many dietary supplements lack evidence, may contain unapproved or hidden drugs, and pose safety and regulatory risks.Nootropics: Drugs vs Dietary Supplements for Brain Health. Operation Supplement Safety. https://www.opss.org/article/nootropics-drugs- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, it would be impossible for language, relationships, or personal identity to develop. Memory loss is usually described as forgetfulness or amnesia. Memory is often understood as an informational processing system with explicit and implicit functioning that is made up of a sensory processor, short-term (or working) memory, and long-term memory. This can be related to the neuron. The sensory processor allows information from the outside world to be sensed in the form of chemical and physical stimuli and attended to various levels of focus and intent. Working memory serves as an encoding and retrieval processor. Information in the form of stimuli is encoded in accordance with explicit or implicit functions by the working memory p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
