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Xaliproden
Xaliproden (codenamed SR57746) is a drug which acts as a 5HT1A agonist. It has neurotrophic and neuroprotective effects ''in vitro'', and has been proposed for use in the treatment of several neurodegenerative conditions including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Development of xaliproden for these two indications was discontinued in 2007 following analysis of Phase III data. While the drug did show an effect on hippocampal volume (suggesting perhaps a slowing of cell loss), there was insufficient evidence for efficacy in counteracting Alzheimer's related cognitive decline. Similarly while there were some indicators of efficacy in ALS, including a small but clinically noteworthy effect on some functional parameters, the overall benefit did not reach statistical significance when results across several Phase III trials were averaged. Xaliproden remains under investigation for treatment of chemotherapy-induced peripheral neuropathy. Paliroden was ...
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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 receptor ag ...
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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
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In Vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from ''in vitro'' experiments may not fully or accurately predict the effects on a whole organism. In contrast to ''in vitro'' experiments, '' in vivo'' studies are those conducted in living organisms, including humans, and whole plants. Definition ''In vitro'' ( la, in glass; often not italicized in English usage) studies are conducted using components of an organism that have been isolated ...
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British Journal Of Pharmacology
The ''British Journal of Pharmacology'' is a biweekly peer-reviewed medical journal covering all aspects of experimental pharmacology. It is published for the British Pharmacological Society by Wiley-Blackwell. It was established in 1946 as the ''British Journal of Pharmacology and Chemotherapy''. The journal obtained its current title in 1968. The current editor-in-chief is Amrita Ahluwalia. Previous editors-in-chief include Ian McGrath, Humphrey Rang, Alan North, Phil Moore, Bill Large, and Tony Birmingham. A sister journal, also published for the British Pharmacological Society by Wiley-Blackwell is the '' British Journal of Clinical Pharmacology''. The journal publishes research papers, review articles, commentaries and correspondence in all fields of pharmacology. It also publishes themed issues, as well as supplements. ''The Concise Guide to PHARMACOLOGY'' The ''Concise Guide to PHARMACOLOGY'' is a supplement of the ''British Journal of Pharmacology'', replacing the "Gu ...
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Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common type of motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. ''Limb-onset ALS'' begins with weakness in the arms or legs, while ''bulbar-onset ALS'' begins with difficulty speaking or swallowing. Half of the people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Most people experience pain. The affected muscles are responsible for chewing food, speaking, and walking. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. ALS eventually causes paralysis and early death, usually from respiratory failure. Most cases of ALS ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of APOE. Other risk factors include a history of head injury, clinical depression, and high blood pre ...
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Clinical Trials
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary ...
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Hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper (also called ''Ammon's horn''), and the dentate gyrus. In Alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result f ...
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Statistical Significance
In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the probability of the study rejecting the null hypothesis, given that the null hypothesis is true; and the ''p''-value of a result, ''p'', is the probability of obtaining a result at least as extreme, given that the null hypothesis is true. The result is statistically significant, by the standards of the study, when p \le \alpha. The significance level for a study is chosen before data collection, and is typically set to 5% or much lower—depending on the field of study. In any experiment or observation that involves drawing a sample from a population, there is always the possibility that an observed effect would have occurred due to sampling error alone. But if the ''p''-value of an observed effect is less than (or equal to) the significa ...
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Cancer Pain
Pain in cancer may arise from a tumor compressing or infiltrating nearby body parts; from treatments and diagnostic procedures; or from skin, nerve and other changes caused by a hormone imbalance or immune response. Most chronic (long-lasting) pain is caused by the illness and most acute (short-term) pain is caused by treatment or diagnostic procedures. However, radiotherapy, surgery and chemotherapy may produce painful conditions that persist long after treatment has ended. The presence of pain depends mainly on the location of the cancer and the stage of the disease. At any given time, about half of all people diagnosed with malignant cancer are experiencing pain, and two-thirds of those with advanced cancer experience pain of such intensity that it adversely affects their sleep, mood, social relations and activities of daily living. With competent management, cancer pain can be eliminated or well controlled in 80% to 90% of cases, but nearly 50% of cancer patients in the dev ...
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Dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affects a person's ability to function and carry out everyday activities. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Consciousness is not affected. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning, and a greater cognitive decline than what is caused by normal aging. Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, ...
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