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Arketamine
Arketamine (developmental code names PCN-101, HR-071603), also known as (''R'')-ketamine or (''R'')-(−)-ketamine, is the (''R'')-(−) enantiomer of ketamine. Similarly to racemic ketamine and esketamine, the ''S''(+) enantiomer of ketamine, arketamine is biologically active; however, it is less potent as an NMDA receptor antagonist and anesthetic and thus has never been approved or marketed for clinical use as an enantiopure drug. Arketamine is currently in clinical development as a novel antidepressant. Relative to esketamine, arketamine possesses 4 to 5 times lower affinity for the PCP site of the NMDA receptor. In accordance, arketamine is significantly less potent than racemic ketamine and especially esketamine in terms of anesthetic, analgesic, and sedative-hypnotic effects. Racemic ketamine has weak affinity for the sigma receptor, where it acts as an agonist, whereas esketamine binds negligibly to this receptor, and so the sigma receptor activity of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
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] [Amazon] |
Sigma Receptor
Sigma receptors (σ-receptors) are protein 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 EXPERA domain protein 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 found to have no structur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Abuse Potential
Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions of drug misuse are used in public health, medical, and criminal justice contexts. In some cases, criminal or anti-social behavior occurs when some persons are under the influence of a drug, and may result in long-term personality changes in individuals which may also occur. In addition to possible physical, social, and psychological harm, the use of some drugs may also lead to criminal penalties, although these vary widely depending on the local jurisdiction.. Drugs most often associated with this term include alcohol, amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, hallucinogens, methaqualone, and opioids. The exact cause of substance abuse is sometimes clear, but there are two predominant theories: either a genetic pre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Psychotomimetic
A drug with psychotomimetic (also known as psychomimetic or 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Reward System
The reward system (the mesocorticolimbic circuit) is a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), associative learning (primarily positive reinforcement and classical conditioning), and positively-valenced emotions, particularly ones involving pleasure as a core component (e.g., joy, euphoria and ecstasy). Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding. The reward system motivates animals to approach stimuli or engage in behaviour that increase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Prepulse Inhibition
Prepulse inhibition (PPI) is a neurological phenomenon in which a weaker prestimulus (prepulse) inhibits the reaction of an organism to a subsequent strong reflex-eliciting stimulus (pulse), often using the startle reflex. The stimuli are usually acoustic, but tactile stimuli (e.g. via air puffs onto the skin) and light stimuli are also used. When prepulse inhibition is high, the corresponding one-time startle response is reduced. The reduction of the amplitude of startle reflects the ability of the nervous system to temporarily adapt to a strong sensory stimulus when a preceding weaker signal is given to warn the organism. PPI is detected in numerous species including mice and humans. Although the extent of the adaptation affects numerous systems, the most comfortable to measure are the muscular reactions, which are normally diminished as a result of the nervous inhibition. Deficits of prepulse inhibition manifest in the inability to filter out the unnecessary information; they h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Hyperlocomotion
Locomotor activity is a measure of animal behavior which is employed in scientific research. Hyperlocomotion, also known as locomotor hyperactivity, hyperactivity, or increased locomotor activity, is an effect of certain drugs in animals in which locomotor activity (locomotion) is increased. It is induced by certain drugs like psychostimulants and NMDA receptor antagonists and is reversed by certain other drugs like antipsychotics and certain antidepressants. Stimulation of locomotor activity is thought to be mediated by increased signaling in the nucleus accumbens, a major brain area involved in behavioral activation and motivated behavior. Hypolocomotion, also known as locomotor hypoactivity, hypoactivity, and decreased locomotor activity, is an effect of certain drugs in animals in which locomotor activity is decreased. It is a characteristic effect of many sedative agents and general anesthetics. Antipsychotics, which are dopamine receptor antagonists, and many serotonerg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Animal Testing On Rodents
Rodents have been employed in biomedical experimentation from the 1650s. Rodent studies up to the early 19th century were mainly physiological or toxicological. The first rodent behavioral study was carried out in 1822, a purely observational study, while quantitative rodent behavioral testing began in the late 19th century. Currently, rodents are commonly used in animal testing for physiological, pathological and behavioral scientific studies, particularly laboratory mouse, mice and laboratory rat, rats, but also guinea pigs, hamsters, gerbils and others. Mice are the most commonly used vertebrate species, due to their availability, size, low cost, ease of handling, and fast Net reproduction rate, reproduction rate. __TOC__ Statistics In the UK in 2015, there were 3.33 million procedures on rodents (80% of total procedures that year). The most common species used were mice (3.03 million procedures, or 73% of the total) and rats (268,522, or 6.5%). Other rodents species included ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Preclinical Research
In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug safety data are collected, typically in laboratory animals. The main goals of preclinical studies are to determine a starting, safe dose for first-in-human study and assess potential toxicity of the product, which typically include new medical devices, prescription drugs, and diagnostics. Companies use stylized statistics to illustrate the risks in preclinical research, such as that on average, only one in every 5,000 compounds that enters drug discovery to the stage of preclinical development becomes an approved drug. Types Each class of product may undergo different types of preclinical research. For instance, drugs may undergo pharmacodynamics (what the drug does to the body) (PD), pharmacokinetics (what the body does to t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Muscarinic Acetylcholine Receptor
Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers. They are mainly found in the parasympathetic nervous system, but also have a role in the sympathetic nervous system in the control of Sweat gland, sweat glands. Muscarinic receptors are so named because they are more sensitive to muscarine than to nicotine. Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system. Many drugs and other substances (for example pilocarpine and Hyoscine hydrobromide, scopolamine) manipulate these two distinct receptors by acting as selective agonists or receptor antagonist, antagonists. Function acetylcholine, Ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Dopamine Reuptake Inhibitor
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission. DRIs are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy for their psychostimulant effects, and in the treatment of obesity and binge eating disorder for their appetite suppressant effects. They are sometimes used as antidepressants in the treatment of mood disorders, but their use as antidepressants is limited given that strong DRIs have a high abuse potential and legal restrictions on their use. Lack of dopamine reuptake and the increase in extracellular levels of dopamine have been l ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Dopamine Transporter
The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine into Vesicle (biology and chemistry), vesicles for storage and later release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter. DAT is implicated in a number of dopamine-related disorders, including ADHD, attention deficit hyperactivity disorder, bipolar disorder, clinical depression, eating disorders, and substance use disorders. The gene that encodes the DAT protein is located on chromosome 5, consists of 15 coding exons, and is roughly 64 base pair#Length measuremen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
