G-protein-coupled NEUROPEPTIDE RECEPTORS that have specificity for OREXINS and play a role in appetite control, and sleep-wake cycles. Two principle receptor types exist, each having a specificity for OREXIN A and OREXIN B peptide subtypes.
Cell surface receptors that bind specific neuropeptides with high affinity and trigger intracellular changes influencing the behavior of cells. Many neuropeptides are also hormones outside of the nervous system.
'Benzoxazoles' are heterocyclic organic compounds, consisting of a benzene ring fused to an oxazole ring, which have been studied for their potential pharmacological activities including anti-inflammatory, analgesic, and antipyretic effects.
Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Area in the hypothalamus bounded medially by the mammillothalamic tract and the anterior column of the FORNIX (BRAIN). The medial edge of the INTERNAL CAPSULE and the subthalamic region form its lateral boundary. It contains the lateral hypothalamic nucleus, tuberomammillary nucleus, lateral tuberal nuclei, and fibers of the MEDIAL FOREBRAIN BUNDLE.
A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and AMNESIA. CATAPLEXY; SLEEP PARALYSIS, and hypnagogic HALLUCINATIONS frequently accompany narcolepsy. The pathophysiology of this disorder includes sleep-onset rapid eye movement (REM) sleep, which normally follows stage III or IV sleep. (From Neurology 1998 Feb;50(2 Suppl 1):S2-S7)
Small, nonspecific nerve cells scattered in the periventricular GRAY MATTER, separating the medial part of the thalamus from the EPENDYMA of the THIRD VENTRICLE. The group includes the paraventricular nucleus, paratenial nucleus, reuniens nucleus, rhomboidal nucleus, and subfascular nucleus.
Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli.
Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.
A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.
Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. (1/269)

Narcolepsy is a disabling sleep disorder affecting humans and animals. It is characterized by daytime sleepiness, cataplexy, and striking transitions from wakefulness into rapid eye movement (REM) sleep. In this study, we used positional cloning to identify an autosomal recessive mutation responsible for this sleep disorder in a well-established canine model. We have determined that canine narcolepsy is caused by disruption of the hypocretin (orexin) receptor 2 gene (Hcrtr2). This result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for narcoleptic patients.  (+info)

Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. (2/269)

Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep regulation. Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only known monogenic model of narcolepsy. Moreover, modafinil, an anti-narcoleptic drug with ill-defined mechanisms of action, activates orexin-containing neurons. We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.  (+info)

Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR. (3/269)

The cellular mechanisms underlying the physiological effects of the orexins are poorly understood. Therefore, the pharmacology of the recombinant human orexin receptors was studied using FLIPR. Intracellular calcium ([Ca2+]i) was monitored in Chinese hamster ovary (CHO) cells stably expressing orexin-1 (OX1) or orexin-2 (OX2) receptors using Fluo-3AM. Orexin-A and orexin-B increased [Ca2+]i in a concentration dependent manner in CHO-OX1 (pEC50=8.03+/-0.08 and 7. 30+/-0.08 respectively, n=5) and CHO-OX2 (pEC50=8.18+/-0.10 and 8. 43+/-0.09 respectively, n=5) cells. This response was typified as a rapid peak in [Ca2+]i (maximal at 6 - 8 s), followed by a gradually declining secondary phase. Thapsigargin (3 microM) or U73122 (3 microM) abolished the response. In calcium-free conditions the peak response was unaffected but the secondary phase was shortened, returning to basal values within 90 s. Calcium (1.5 mM) replacement restored the secondary phase. In conclusion, orexins cause a phospholipase C-mediated release of calcium from intracellular stores, with subsequent calcium influx.  (+info)

Orexin synthesis and response in the gut. (4/269)

Orexin (hypocretin) appears to play a role in the regulation of energy balances. Previous reports have indicated that orexin-containing neurons are found only in the lateral hypothalamic (LH) area. We show that a subset of neurons in the gut which also express leptin receptors display orexin-like immunoreactivity and express functional orexin receptors. Orexin excites secretomotor neurons in the guinea pig submucosal plexus and increases motility. Moreover, fasting upregulates the phosphorylated form of cAMP response element-binding protein (pCREB) in orexin-immunoreactive neurons, indicating a functional response to food status in these cells. Together, these data suggest that orexin in the gut may play an even more intimate role in regulating energy homeostasis than it does in the CNS.  (+info)

The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors. (5/269)

The pharmacology of the orexin-like peptides, hypocretin-1 and hypocretin-2, was studied in Chinese hamster ovary (CHO) cells stably expressing orexin-1 (OX(1)) or orexin-2 (OX(2)) receptors by measuring intracellular calcium ([Ca(2+)](i)) using Fluo-3AM. Orexin-A and orexin-B increased [Ca(2+)](i) in CHO-OX(1) (pEC(50)=7. 99+/-0.05 and 7.00+/-0.10 respectively, n=8) and CHO-OX(2) (pEC(50)=8.30+/-0.05 and 8.21+/-0.07 respectively, n=5). However, hypocretin-1 and hypocretin-2 were markedly less potent, with pEC(50) values of 5.31+/-0.04 and 5.41+/-0.04 respectively in CHO-OX(2) cells (n=5). In CHO-OX(1) cells 10 microM hypocretin-1 only elicited a 37.5+/-3.4% response whilst 10 microM hypocretin-2 elicited a 18.0+/-2.1% response (n=8). Desensitisation of OX(1) or OX(2) with orexin-A (100 nM) abolished the response to orexin-A (10 nM) and the hypocretins (10 microM), but not to UTP (3 microM). In conclusion, the hypocretins are only weak agonists at the orexin receptors.  (+info)

The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C. (6/269)

Ca(2+) elevations in Chinese hamster ovary cells stably expressing OX(1) receptors were measured using fluorescent Ca(2+) indicators fura-2 and fluo-3. Stimulation with orexin-A led to pronounced Ca(2+) elevations with an EC(50) around 1 nm. When the extracellular [Ca(2+)] was reduced to a submicromolar concentration, the EC(50) was increased 100-fold. Similarly, the inositol 1,4,5-trisphosphate production in the presence of 1 mm external Ca(2+) was about 2 orders of magnitude more sensitive to orexin-A stimulation than in low extracellular Ca(2+). The shift in the potency was not caused by depletion of intracellular Ca(2+) but by a requirement of extracellular Ca(2+) for production of inositol 1,4,5-trisphosphate. Fura-2 experiments with the "Mn(2+)-quench technique" indicated a direct activation of a cation influx pathway by OX(1) receptor independent of Ca(2+) release or pool depletion. Furthermore, depolarization of the cells to +60 mV, which almost nullifies the driving force for Ca(2+) entry, abolished the Ca(2+) response to low concentrations of orexin-A. The results thus suggest that OX(1) receptor activation leads to two responses, (i) a Ca(2+) influx and (ii) a direct stimulation of phospholipase C, and that these two responses converge at the level of phospholipase C where the former markedly enhances the potency of the latter.  (+info)

Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. (7/269)

The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat are produced by approximately 1200 neurons whose cell bodies are located in the lateral hypothalamus. The hypocretins/orexins have been implicated in the regulation of rapid eye movement (REM) sleep and the pathophysiology of narcolepsy. In the present study, we investigated whether the locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be a target for hcrt to regulate REM sleep. Local administration of hcrt1 but not hcrt2 in the LC suppressed REM sleep in a dose-dependent manner and increased wakefulness at the expense of deep, slow-wave sleep. These effects were blocked with an antibody that neutralizes hcrt binding to hcrt receptor 1. In situ hybridization and immunocytochemistry showed the presence of hcrt receptor 1 but not the presence of hcrt receptor 2 in the LC. Iontophoretic application of hcrt1 enhanced the firing rate of LC neurons in vivo, and local injection of hcrt1 into the LC induced the expression of c-fos in the LC area. We propose that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.  (+info)

Distribution of OX2 antigen and OX2 receptor within retina. (8/269)

PURPOSE: OX2 is a member of the immunoglobulin superfamily expressed on a broad range of tissues including neurons of the central and peripheral nervous systems, thymocytes, and endothelium. The recently identified OX2 receptor (OX2R) is restricted to the surfaces of myeloid lineage cells, including microglia. Functional data have implicated the OX2-OX2R interaction as a myeloid downregulatory signal. The purpose of this study was to determine the distribution and extent of expression of OX2 and its receptor within the retina, a tissue developed to restrain immune-mediated inflammatory damage. METHODS: OX2 and OX2R monoclonal antibodies (mAbs) were used to determine OX2 and OX2R protein expression, respectively, by flow cytometry of isolated myeloid-derived cells from normal and inflamed rat retina and by immunohistochemistry of serial sections of rat retina. For comparison, distribution of OX2 was documented using species-specific monoclonal antibodies in mouse and human retina. No OX2R mAbs are available for mouse or human detection. RESULTS: OX2 was expressed on retinal vascular endothelium and glial fibrillary acidic protein (GFAP)-negative neurons in retina and optic nerve and on a subpopulation of CD45(+) perivascular and juxtavascular cells. Within normal retina, OX2R was not detected on myeloid-derived cells. During experimental autoimmune uveoretinitis (EAU), expression of both OX2 and OX2R was noted on infiltrating leukocytes. CONCLUSIONS: Taking these results of the distribution of OX2 in normal and OX2R in inflamed retina with other functional data of OX2-OX2R interaction, it is suggested that the OX2-OX2R interaction has the potential to contribute to a novel pathway that suppresses and limits immunologic inflammatory damage within the retina.  (+info)

Orexin receptors are a type of G protein-coupled receptor found in the central nervous system that play a crucial role in regulating various physiological functions, including wakefulness, energy balance, and reward processing. There are two subtypes of orexin receptors: OX1R (orexin-1 receptor) and OX2R (orexin-2 receptor). These receptors bind to the neuropeptides orexin A and orexin B, which are synthesized in a small group of neurons located in the hypothalamus. Activation of these receptors leads to increased wakefulness, appetite stimulation, and reward-seeking behavior, among other effects. Dysregulation of the orexin system has been implicated in several neurological disorders, such as narcolepsy, where a loss of orexin-producing neurons results in excessive daytime sleepiness and cataplexy.

Neuropeptide receptors are a type of cell surface receptor that bind to neuropeptides, which are small signaling molecules made up of short chains of amino acids. These receptors play an important role in the nervous system by mediating the effects of neuropeptides on various physiological processes, including neurotransmission, pain perception, and hormone release.

Neuropeptide receptors are typically composed of seven transmembrane domains and are classified into several families based on their structure and function. Some examples of neuropeptide receptor families include the opioid receptors, somatostatin receptors, and vasoactive intestinal peptide (VIP) receptors.

When a neuropeptide binds to its specific receptor, it activates a signaling pathway within the cell that leads to various cellular responses. These responses can include changes in gene expression, ion channel activity, and enzyme function. Overall, the activation of neuropeptide receptors helps to regulate many important functions in the body, including mood, appetite, and pain sensation.

Benzoxazoles are a class of heterocyclic organic compounds that consist of a benzene ring fused to an oxazole ring. The term "benzoxazoles" generally refers to the parent compound, but it can also refer to its derivatives that contain various functional groups attached to the benzene and/or oxazole rings.

Benzoxazoles have a wide range of applications in the pharmaceutical industry, as they are used in the synthesis of several drugs with anti-inflammatory, antifungal, and antiviral properties. They also have potential uses in materials science, such as in the development of organic light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs).

It is worth noting that benzoxazoles themselves are not used in medical treatments or therapies. Instead, their derivatives with specific functional groups and structures are designed and synthesized to have therapeutic effects on various diseases and conditions.

Neuropeptides are small protein-like molecules that are used by neurons to communicate with each other and with other cells in the body. They are produced in the cell body of a neuron, processed from larger precursor proteins, and then transported to the nerve terminal where they are stored in secretory vesicles. When the neuron is stimulated, the vesicles fuse with the cell membrane and release their contents into the extracellular space.

Neuropeptides can act as neurotransmitters or neuromodulators, depending on their target receptors and the duration of their effects. They play important roles in a variety of physiological processes, including pain perception, appetite regulation, stress response, and social behavior. Some neuropeptides also have hormonal functions, such as oxytocin and vasopressin, which are produced in the hypothalamus and released into the bloodstream to regulate reproductive and cardiovascular function, respectively.

There are hundreds of different neuropeptides that have been identified in the nervous system, and many of them have multiple functions and interact with other signaling molecules to modulate neural activity. Dysregulation of neuropeptide systems has been implicated in various neurological and psychiatric disorders, such as chronic pain, addiction, depression, and anxiety.

G-protein-coupled receptors (GPCRs) are a family of membrane receptors that play an essential role in cellular signaling and communication. These receptors possess seven transmembrane domains, forming a structure that spans the lipid bilayer of the cell membrane. They are called "G-protein-coupled" because they interact with heterotrimeric G proteins upon activation, which in turn modulate various downstream signaling pathways.

When an extracellular ligand binds to a GPCR, it causes a conformational change in the receptor's structure, leading to the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the associated G protein's α subunit. This exchange triggers the dissociation of the G protein into its α and βγ subunits, which then interact with various effector proteins to elicit cellular responses.

There are four main families of GPCRs, classified based on their sequence similarities and downstream signaling pathways:

1. Gq-coupled receptors: These receptors activate phospholipase C (PLC), which leads to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
2. Gs-coupled receptors: These receptors activate adenylyl cyclase, which increases the production of cyclic adenosine monophosphate (cAMP) and subsequently activates protein kinase A (PKA).
3. Gi/o-coupled receptors: These receptors inhibit adenylyl cyclase, reducing cAMP levels and modulating PKA activity. Additionally, they can activate ion channels or regulate other signaling pathways through the βγ subunits.
4. G12/13-coupled receptors: These receptors primarily activate RhoGEFs, which in turn activate RhoA and modulate cytoskeletal organization and cellular motility.

GPCRs are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and sensory perception. Dysregulation of GPCR function has been implicated in numerous diseases, making them attractive targets for drug development.

Intracellular signaling peptides and proteins are molecules that play a crucial role in transmitting signals within cells, which ultimately lead to changes in cell behavior or function. These signals can originate from outside the cell (extracellular) or within the cell itself. Intracellular signaling molecules include various types of peptides and proteins, such as:

1. G-protein coupled receptors (GPCRs): These are seven-transmembrane domain receptors that bind to extracellular signaling molecules like hormones, neurotransmitters, or chemokines. Upon activation, they initiate a cascade of intracellular signals through G proteins and secondary messengers.
2. Receptor tyrosine kinases (RTKs): These are transmembrane receptors that bind to growth factors, cytokines, or hormones. Activation of RTKs leads to autophosphorylation of specific tyrosine residues, creating binding sites for intracellular signaling proteins such as adapter proteins, phosphatases, and enzymes like Ras, PI3K, and Src family kinases.
3. Second messenger systems: Intracellular second messengers are small molecules that amplify and propagate signals within the cell. Examples include cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), diacylglycerol (DAG), inositol triphosphate (IP3), calcium ions (Ca2+), and nitric oxide (NO). These second messengers activate or inhibit various downstream effectors, leading to changes in cellular responses.
4. Signal transduction cascades: Intracellular signaling proteins often form complex networks of interacting molecules that relay signals from the plasma membrane to the nucleus. These cascades involve kinases (protein kinases A, B, C, etc.), phosphatases, and adapter proteins, which ultimately regulate gene expression, cell cycle progression, metabolism, and other cellular processes.
5. Ubiquitination and proteasome degradation: Intracellular signaling pathways can also control protein stability by modulating ubiquitin-proteasome degradation. E3 ubiquitin ligases recognize specific substrates and conjugate them with ubiquitin molecules, targeting them for proteasomal degradation. This process regulates the abundance of key signaling proteins and contributes to signal termination or amplification.

In summary, intracellular signaling pathways involve a complex network of interacting proteins that relay signals from the plasma membrane to various cellular compartments, ultimately regulating gene expression, metabolism, and other cellular processes. Dysregulation of these pathways can contribute to disease development and progression, making them attractive targets for therapeutic intervention.

The lateral hypothalamic area (LHA) is a region in the hypothalamus, which is a part of the brain that plays a crucial role in regulating various autonomic functions and maintaining homeostasis. The LHA is located laterally to the third ventricle and contains several neuronal populations that are involved in diverse physiological processes such as feeding behavior, energy balance, sleep-wake regulation, and neuroendocrine function.

Some of the key neurons found in the LHA include orexin/hypocretin neurons, melanin-concentrating hormone (MCH) neurons, and agouti-related protein (AGRP) neurons. These neurons release neurotransmitters and neuropeptides that modulate various physiological functions, including appetite regulation, energy expenditure, and arousal. Dysfunction in the LHA has been implicated in several neurological and psychiatric disorders, such as narcolepsy, obesity, and depression.

Narcolepsy is a chronic neurological disorder that affects the control of sleep and wakefulness. It's characterized by excessive daytime sleepiness (EDS), where people experience sudden, uncontrollable episodes of falling asleep during the day. These "sleep attacks" can occur at any time - while working, talking, eating, or even driving.

In addition to EDS, narcolepsy often includes cataplexy, a condition that causes loss of muscle tone, leading to weakness and sometimes collapse, often triggered by strong emotions like laughter or surprise. Other common symptoms are sleep paralysis (a temporary inability to move or speak while falling asleep or waking up), vivid hallucinations during the transitions between sleep and wakefulness, and fragmented nighttime sleep.

The exact cause of narcolepsy is not fully understood, but it's believed to involve genetic and environmental factors, as well as problems with certain neurotransmitters in the brain, such as hypocretin/orexin, which regulate sleep-wake cycles. Narcolepsy can significantly impact a person's quality of life, making it essential to seek medical attention for proper diagnosis and management.

The midline thalamic nuclei are a group of nuclei located in the thalamus, which is a part of the diencephalon in the brain. The thalamus serves as a relay station for sensory and motor signals to the cerebral cortex. The midline thalamic nuclei are situated in the most medial portion of the thalamus, along the midline. They include several distinct nuclei, such as the paraventricular nucleus, the reuniens nucleus, the rhomboid nucleus, and the central medial nucleus. These nuclei have complex connections with various brain regions, including the hypothalamus, the hippocampus, and the prefrontal cortex. They are involved in a variety of functions, such as memory, emotion, and sleep regulation.

Acetamides are organic compounds that contain an acetamide functional group, which is a combination of an acetyl group (-COCH3) and an amide functional group (-CONH2). The general structure of an acetamide is R-CO-NH-CH3, where R represents the rest of the molecule.

Acetamides are found in various medications, including some pain relievers, muscle relaxants, and anticonvulsants. They can also be found in certain industrial chemicals and are used as intermediates in the synthesis of other organic compounds.

It is important to note that exposure to high levels of acetamides can be harmful and may cause symptoms such as headache, dizziness, nausea, and vomiting. Chronic exposure has been linked to more serious health effects, including liver and kidney damage. Therefore, handling and use of acetamides should be done with appropriate safety precautions.

Wakefulness is a state of consciousness in which an individual is alert and aware of their surroundings. It is characterized by the ability to perceive, process, and respond to stimuli in a purposeful manner. In a medical context, wakefulness is often assessed using measures such as the electroencephalogram (EEG) to evaluate brain activity patterns associated with consciousness.

Wakefulness is regulated by several interconnected neural networks that promote arousal and attention. These networks include the ascending reticular activating system (ARAS), which consists of a group of neurons located in the brainstem that project to the thalamus and cerebral cortex, as well as other regions involved in regulating arousal and attention, such as the basal forebrain and hypothalamus.

Disorders of wakefulness can result from various underlying conditions, including neurological disorders, sleep disorders, medication side effects, or other medical conditions that affect brain function. Examples of such disorders include narcolepsy, insomnia, hypersomnia, and various forms of encephalopathy or brain injury.

The hypothalamus is a small, vital region of the brain that lies just below the thalamus and forms part of the limbic system. It plays a crucial role in many important functions including:

1. Regulation of body temperature, hunger, thirst, fatigue, sleep, and circadian rhythms.
2. Production and regulation of hormones through its connection with the pituitary gland (the hypophysis). It controls the release of various hormones by producing releasing and inhibiting factors that regulate the anterior pituitary's function.
3. Emotional responses, behavior, and memory formation through its connections with the limbic system structures like the amygdala and hippocampus.
4. Autonomic nervous system regulation, which controls involuntary physiological functions such as heart rate, blood pressure, and digestion.
5. Regulation of the immune system by interacting with the autonomic nervous system.

Damage to the hypothalamus can lead to various disorders like diabetes insipidus, growth hormone deficiency, altered temperature regulation, sleep disturbances, and emotional or behavioral changes.

Urea is not a medical condition but it is a medically relevant substance. Here's the definition:

Urea is a colorless, odorless solid that is the primary nitrogen-containing compound in the urine of mammals. It is a normal metabolic end product that is excreted by the kidneys and is also used as a fertilizer and in various industrial applications. Chemically, urea is a carbamide, consisting of two amino groups (NH2) joined by a carbon atom and having a hydrogen atom and a hydroxyl group (OH) attached to the carbon atom. Urea is produced in the liver as an end product of protein metabolism and is then eliminated from the body by the kidneys through urination. Abnormal levels of urea in the blood, known as uremia, can indicate impaired kidney function or other medical conditions.

Isoquinolines are not a medical term per se, but a chemical classification. They refer to a class of organic compounds that consist of a benzene ring fused to a piperidine ring. This structure is similar to that of quinoline, but with the nitrogen atom located at a different position in the ring.

Isoquinolines have various biological activities and can be found in some natural products, including certain alkaloids. Some isoquinoline derivatives have been developed as drugs for the treatment of various conditions, such as cardiovascular diseases, neurological disorders, and cancer. However, specific medical definitions related to isoquinolines typically refer to the use or effects of these specific drugs rather than the broader class of compounds.

Sleep is a complex physiological process characterized by altered consciousness, relatively inhibited sensory activity, reduced voluntary muscle activity, and decreased interaction with the environment. It's typically associated with specific stages that can be identified through electroencephalography (EEG) patterns. These stages include rapid eye movement (REM) sleep, associated with dreaming, and non-rapid eye movement (NREM) sleep, which is further divided into three stages.

Sleep serves a variety of functions, including restoration and strengthening of the immune system, support for growth and development in children and adolescents, consolidation of memory, learning, and emotional regulation. The lack of sufficient sleep or poor quality sleep can lead to significant health problems, such as obesity, diabetes, cardiovascular disease, and even cognitive decline.

The American Academy of Sleep Medicine (AASM) defines sleep as "a period of daily recurring natural rest during which consciousness is suspended and metabolic processes are reduced." However, it's important to note that the exact mechanisms and purposes of sleep are still being researched and debated among scientists.

Hypnotics and sedatives are classes of medications that have depressant effects on the central nervous system, leading to sedation (calming or inducing sleep), reduction in anxiety, and in some cases, decreased awareness or memory. These agents work by affecting the neurotransmitter GABA (gamma-aminobutyric acid) in the brain, which results in inhibitory effects on neuronal activity.

Hypnotics are primarily used for the treatment of insomnia and other sleep disorders, while sedatives are often prescribed to manage anxiety or to produce a calming effect before medical procedures. Some medications can function as both hypnotics and sedatives, depending on the dosage and specific formulation. Common examples of these medications include benzodiazepines (such as diazepam and lorazepam), non-benzodiazepine hypnotics (such as zolpidem and eszopiclone), barbiturates, and certain antihistamines.

It is essential to use these medications under the guidance of a healthcare professional, as they can have potential side effects, such as drowsiness, dizziness, confusion, and impaired coordination. Additionally, long-term use or high doses may lead to tolerance, dependence, and withdrawal symptoms upon discontinuation.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

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