|
Repinotan Dose Relationship To Nociception
Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects. History Bayer Healthcare AG (Wuppertal, Germany) first synthesized repinotan during early 2000s. As of 2004, it was expected to be filed by the NDA. Phase III trials for both ischemic stroke and traumatic brain injury were run in March 2002. However, these trials found the drug ineffective as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Binding Selectivity
Binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Binding selectivity is of major importance in biochemistry and in chemical separation processes. Selectivity coefficient The concept of selectivity is used to quantify the extent to which one chemical substance, A, binds each of two other chemical substances, B and C. The simplest case is where the complexes formed have 1:1 stoichiometry. Then, the two interactions may be characterized by equilibrium constants ''K''AB and ''K''AC.The constant used here are ''association'' constants. ''Dissociation'' constants are used in some contexts. A dissociation constant is the reciprocal of an association constant. : + B AB; \mathit K_ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-HT1A Receptor
The serotonin 1A receptor (or 5-HT1A receptor) is a subtype of serotonin receptor, or 5-HT receptor, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarisation and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene. Distribution The 5-HT1A receptor is the most widespread of all the 5-HT receptors. In the central nervous system, 5-HT1A receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucleus in high densities, while low amounts also exist in the basal ganglia and thalamus. The 5-HT1A receptors in the raphe nucleus are largely somatodendritic autoreceptors, whereas those in other areas such as the hippocampus are postsynaptic receptors. Function Neuromodulation 5-HT1A recepto ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Full Agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist. Etymology From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive Types of agonists can be activated by either endogenous agonists (such as |
Neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption (i.e. methamphetamine overdoses). Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control. The main risk factor for stroke is high blood pressure. Other risk factors include high blood cholesterol, tobacco smoking, obesity, diabetes mellitus, a previous TIA, end-st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Respiratory Depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. Hypoventilation is not synonymous with respiratory arrest, in which breathing ceases entirely and death occurs within minutes due to hypoxia and leads rapidly into complete anoxia, although both are medical emergencies. Hypoventilation can be considered a precursor to hypoxia and its lethality is attributed to hypoxia with carbon dioxide toxicity. Causes Hypoventilation may be caused by: *A medical condition such as stroke affecting the brainstem *Voluntary breath-holding or underbreathing, for example, hypoventilation training or the Buteyko method. *Medication or drugs, typically when taken in accidental or intentional overdose. Opioids and benzodiazepines in particular are known to cause respiratory depress ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make other illicit drug, illicit opioids. There are numerous methods used to administer morphine: oral; sublingual administration, sublingual; via inhalation; intramuscular, injection into a muscle; by Subcutaneous injection, injection under the skin; intravenously; Intrathecally, injection into the space around the spinal cord; transdermal; or via rectal administration, rectal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during Ch ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Traumatic Brain Injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic brain injury), mechanism ( closed or penetrating head injury), or other features (e.g., occurring in a specific location or over a widespread area). Head injury is a broader category that may involve damage to other structures such as the scalp and skull. TBI can result in physical, cognitive, social, emotional and behavioral symptoms, and outcomes can range from complete recovery to permanent disability or death. Causes include falls, vehicle collisions and violence. Brain trauma occurs as a consequence of a sudden acceleration or deceleration within the cranium or by a complex combination of both movement and sudden impact. In addition to the damage caused at the moment of injury, a variety of events following the injury may result in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Repinotan Dose Relationship To Nociception
Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects. History Bayer Healthcare AG (Wuppertal, Germany) first synthesized repinotan during early 2000s. As of 2004, it was expected to be filed by the NDA. Phase III trials for both ischemic stroke and traumatic brain injury were run in March 2002. However, these trials found the drug ineffective as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Repinotan Synthesis
Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects. History Bayer Healthcare AG (Wuppertal, Germany) first synthesized repinotan during early 2000s. As of 2004, it was expected to be filed by the NDA. Phase III trials for both ischemic stroke and traumatic brain injury were run in March 2002. However, these trials found the drug ineffective as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Robalzotan
Robalzotan (NAD-299, AZD-7371) is a selective antagonist at the 5-HT1A receptor. It was shown to completely reverse the autoreceptor-mediated inhibition of serotonin release induced by the administration of selective serotonin reuptake inhibitors like citalopram in rodent studies. It was subsequently investigated by AstraZeneca as a potential antidepressant but like many other 5-HT1A ligands was discontinued. Later on it was researched for other indications such as irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ... but was dropped once again. See also * Ebalzotan * UH-301 References Amines Carboxamides Benzopyrans Fluoroarenes Cyclobutyl compounds {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amines
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines). Important amines include amino acids, biogenic amines, trimethylamine, and aniline; Inorganic derivatives of ammonia are also called amines, such as monochloramine (). The substituent is called an amino group. Compounds with a nitrogen atom attached to a carbonyl group, thus having the structure , are called amides and have different chemical properties from amines. Classification of amines Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
