Lisuride
Lysergic Acid Diethylamide
Bulbar Palsy, Progressive
Home Infusion Therapy
Akinetic Mutism
Serotonin 5-HT2 Receptor Antagonists
Serotonin 5-HT2 Receptor Agonists
Receptors, Dopamine D3
Bromocriptine
Serotonin Receptor Agonists
Antiparkinson Agents
Hallucinogens
Antagonism of a PCP drug discrimination by hallucinogens and related drugs. (1/45)
Drugs such as PCP and MK-801 can cause psychotic reactions in humans by antagonizing NMDA receptors. This action is ultimately toxic to certain cortical neurons and may be one mechanism underlying neurodegenerative diseases, including schizophrenia. It has been reported that hallucinogens such as LSD, DOM, and DOI can block the neurotoxic effects of NMDA antagonists, possibly by activating inhibitory 5-HT2A receptors on GABAergic interneurons that normally inhibit glutamatergic projections to the retrosplenial and cingulate cortexes. The purpose of this experiment was to determine the extent to which similar drugs might also alter the behavioral effects of one NMDA antagonist, PCP. Rats were trained to discriminate this compound (2.5 mg/kg) from saline and were then given a series of antagonist tests. It was found that LSD (0.32 mg/kg) and DOM (4.0 mg/kg) blocked the PCP cue completely; DMT (8.0 mg/kg) and a structural congener of LSD, lisuride (LHM; 0.4 mg/kg), blocked the effects of PCP partially. The 5-HT/DA antagonists spiperone and ritanserin had no effect on the PCP cue. These data suggest that LSD, DOM, and, less effectively, DMT and LHM can block the behavioral as well as the neurotoxic effects of NMDA antagonists most likely through agonist actions at 5-HT2 receptors. (+info)Terguride attenuates prolactin levels and ameliorates insulin sensitivity and insulin binding in obese spontaneously hypertensive rats. (2/45)
Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats. (+info)Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state. (3/45)
1. Antipsychotic drugs may mediate their therapeutic effects not only by preventing the binding of dopamine but also by decreasing the propensity of the dopamine receptor to assume an active R* state. Ligand-mediated activation and blockade of the recombinant human D(2long) receptor was investigated in CHO-K1 cells upon modulation of its R* state. 2. Both the Ala(371)Lys (A371K) and Thr(372)Arg (T372R) D2long receptor mutants could be activated in a ligand-dependent manner via a chimeric G(alphaq/o) protein, and more efficaciously so than with the promiscuous G(alpha15) protein. 3. Dopamine and partial agonists (E(max): lisuride >> (+)-UH 232 approximately bromerguride) displayed dissimilar Ca(2+) kinetic properties at wild-type and mutant receptors. A371K and T372R D2long receptor mutants demonstrated an attenuated and enhanced maximal response to these partial agonists, respectively. 4. Dopamine antagonists were unable to block the transient high-magnitude Ca(2+) phase at the wild-type D2long receptor upon simultaneous exposure to antagonist and dopamine, while full blockade of the low-magnitude Ca(2+) phase did occur at a later time (onset-time: haloperidol < bromerguride < (+)-butaclamol). A similar, though more efficacious, antagonist profile was also found at the A371K mutant receptor. Conversely, the blockade of the low-magnitude Ca(2+) phase was attenuated (haloperidol) or almost absent [(+)-butaclamol and bromerguride] at the T372R mutant receptor. 5. In conclusion, mutagenesis of the Ala(371) and Thr(372) positions affects in an opposite way the ligand-dependent activation and blockade of the D2long receptor. The observed attenuation of dopamine-mediated Ca(2+) signal generation with different decay-times may underlie distinct properties of the dopaminergic ligands. (+info)Dopaminergic modulation of grooming behavior in virgin and pregnant rats. (4/45)
Dopamine receptors are involved in the expression of grooming behavior. The pregnancy-induced increase in self-licking observed in rats is important for mammary gland development and lactation. This study focuses on the role of dopamine receptor subtypes in grooming behavior of virgin and pregnant female rats. General and mammary gland grooming were measured in virgin rats treated with 0.25 mg/kg of the D1-like agonist SKF-81297 and antagonist SKF-83566 and the D2-like agonist lisuride and antagonist sulpiride. The effects of 0.01 and 0.25 mg/kg doses of the same agonists and antagonists were evaluated in pregnant rats as well. In virgin animals both SKF-83566 and sulpiride treatments significantly reduced the time spent in general grooming, while none of the dopamine agonists was able to significantly change any parameter of general grooming. Time spent in grooming directed at the mammary glands was not affected significantly by any of the drug treatments in virgin rats. All drugs tested significantly decreased the frequency of and the time spent with general grooming, while SKF-81297 treatment alone did not significantly reduce the duration of mammary gland grooming in pregnant rats. These data show that in female rats the behavioral effects of D1-like and D2-like dopamine receptor stimulation and blockade differ according to physiological state. The results suggest that dopamine receptors may play specific roles modulating grooming behavior in pregnant rats. Since grooming of the mammary gland during pregnancy may influence lactation, this aspect is relevant for studies regarding the perinatal use of dopamine-related drugs. (+info)Dopamine partial agonist reverses amphetamine withdrawal in rats. (5/45)
Decreased motivation to work for a natural reward is a sign of amphetamine withdrawal and is thought to be associated with hypofunction of the mesolimbic dopamine system. During withdrawal from repeated amphetamine administration, rats showed reduced responding for a sweet solution in a progressive ratio schedule. Repeated systemic treatment with terguride (0.2 and 0.4 mg/kg, i.p.) twice daily during the first four days of amphetamine withdrawal reversed the decrease in responding for the sweet solution. These results suggest that dopamine partial agonists, possibly due to their agonistic-like actions under these conditions, are a potential therapeutic approach for the acute withdrawal stage of the amphetamine addition cycle. (+info)Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease. (6/45)
Motor complications are a major source of disability for patients with advanced Parkinson's disease. Surgical therapies provide benefit to some, but these treatments are expensive and associated with adverse effects. Current research indicates that motor complications are associated with abnormal, intermittent, pulsatile stimulation of denervated dopamine receptors using short acting dopaminergic agents such as levodopa. Retrospective studies suggest that the use of longer-acting more continuous dopaminergic therapies can improve both motor fluctuations and dyskinesia. We performed a prospective, long-term (4-year) trial comparing patients randomized to receive subcutaneous infusion of the dopamine agonist lisuride versus conventional therapy with oral levodopa and dopamine agonists. We demonstrate that patients receiving lisuride infusions experienced a significant reduction in both motor fluctuations and dyskinesia compared with patients receiving standard dopaminergic therapies. Benefits persisted for the 4-year duration of the study. Mean Unified Parkinson's Disease Rating Scale scores in "ON" and "OFF" states did not significantly change between baseline and 4 years for patients in the lisuride group, but deteriorated in patients in the levodopa group. This study indicates that continuous lisuride infusion can be beneficial for patients with advanced Parkinson's disease and reverse established motor fluctuations and dyskinesia. (+info)In-vivo SPECT imaging of D2 receptor with iodine-iodolisuride: results in supranuclear palsy. (7/45)
We assessed the potential use of [123I]iodolisuride (ILIS), a new iodine ergolene derivative, to study human striatal D2 dopamine receptors with SPECT. In normal subjects, we found that the tracer accumulated preferentially in striatum. This was prevented by high doses of haloperidol. The striatal accumulation was maximal between 60 and 180 min after injection. The striatum-to-cerebellum radioactivity concentration ratio as an index of specific binding, measured 60 min after injection, was 1.52 +/- 0.19 (mean +/- s.d.) in controls and 1.36 +/- 0.11 in patients with supranuclear palsy (p less than 0.03). Our results show that ILIS may be used to study D2 receptors with SPECT. In-vivo changes of D2 receptors in human brain may be detected with this method. (+info)8R-lisuride is a potent stereospecific histamine H1-receptor partial agonist. (8/45)
The human histamine H1 receptor (H1R) is an important, well characterized target for the development of antagonists to treat allergic conditions. Many neuropsychiatric drugs are known to potently antagonize the H1R, thereby producing some of their side effects. In contrast, the tolerability and potential therapeutic utility of H1R agonism is currently unclear. We have used a cell-based functional assay to evaluate known therapeutics and reference drugs for H1R agonist activity. Our initial functional screen identified three ergot-based compounds possessing heretofore-unknown H1R agonist activity. 8R-lisuride demonstrated potent agonist activity in various assays including receptor selection and amplification technology, inositol phosphate accumulation, and activation of nuclear factor-kappaB with pEC50 values of 8.1, 7.9, and 7.9, respectively, and with varying degrees of efficacy. Based on these assays, 8R-lisuride is the most potent stereospecific partial agonist for the human H1R yet reported. Investigation of the residues involved in histamine and lisuride binding, using H1R mutants and molecular modeling, have revealed that although these ligands are structurally different, the lisuride-binding pocket in the H1R closely corresponds to the histamine-binding pocket. The discovery of a potent stereospecific partial H1R agonist provides a valuable tool to further characterize this important therapeutic target in vitro. (+info)Lisuride is a type of medication called a dopamine agonist, which works by stimulating dopamine receptors in the brain. It is primarily used to treat Parkinson's disease and related disorders, as it can help to alleviate symptoms such as stiffness, tremors, spasms, and poor muscle control.
Lisuride may also be used off-label for other conditions, such as certain types of headaches or cluster headaches. It is available in the form of tablets and is typically taken several times a day, with dosages adjusted based on individual patient needs and responses to treatment.
As with any medication, lisuride can have side effects, including nausea, dizziness, drowsiness, hallucinations, and orthostatic hypotension (low blood pressure upon standing). It is important for patients taking this medication to follow their healthcare provider's instructions carefully and report any unusual symptoms or concerns.
Ergolines are a group of ergot alkaloids that have been widely used in the development of various pharmaceutical drugs. These compounds are known for their ability to bind to and stimulate specific receptors in the brain, particularly dopamine receptors. As a result, they have been explored for their potential therapeutic benefits in the treatment of various neurological and psychiatric conditions, such as Parkinson's disease, migraine, and depression.
However, ergolines can also have significant side effects, including hallucinations, nausea, and changes in blood pressure. In addition, some ergot alkaloids have been associated with a rare but serious condition called ergotism, which is characterized by symptoms such as muscle spasms, vomiting, and gangrene. Therefore, the use of ergolines must be carefully monitored and managed to ensure their safety and effectiveness.
Some specific examples of drugs that contain ergolines include:
* Dihydroergotamine (DHE): used for the treatment of migraine headaches
* Pergolide: used for the treatment of Parkinson's disease
* Cabergoline: used for the treatment of Parkinson's disease and certain types of hormonal disorders
It is important to note that while ergolines have shown promise in some therapeutic areas, they are not without their risks. As with any medication, it is essential to consult with a healthcare provider before using any drug containing ergolines to ensure that it is safe and appropriate for an individual's specific needs.
Lysergic Acid Diethylamide (LSD) is defined in medical terms as a powerful synthetic hallucinogenic drug. It is derived from lysergic acid, which is found in ergot, a fungus that grows on grains such as rye. LSD is typically distributed as a liquid, tablets, or thin squares of gelatin (commonly known as window panes). It is odorless, colorless, and has a slightly bitter taste.
LSD is considered one of the most potent mood-changing chemicals. Its effects, often called a "trip," can be stimulating, pleasurable, and mind-altering or they can lead to an unpleasant, sometimes terrifying experience called a "bad trip." The effects of LSD are unpredictable depending on factors such as the user's personality, mood, expectations, and the environment in which the drug is used.
In the medical field, LSD has been studied for its potential benefits in treating certain mental health conditions, such as anxiety and depression associated with life-threatening illnesses, but further research is needed to establish its safety and efficacy. It's important to note that the use of LSD outside of approved medical settings and supervision is not legal in most countries and can lead to serious legal consequences.
Progressive bulbar palsy (PBP) is a form of motor neuron disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS). It is characterized by the progressive degeneration of the motor neurons in the brainstem, which control vital functions such as swallowing, speaking, chewing, and breathing.
In PBP, these symptoms gradually worsen over time, often resulting in severe disability and ultimately death due to respiratory failure. The progression of the disease can vary from person to person, but it typically advances more slowly than other forms of ALS. There is currently no cure for PBP or any other form of MND, and treatment is focused on managing symptoms and maintaining quality of life.
Home infusion therapy is a healthcare service where patients receive administered medications, fluids, or nutritional support through a vein (intravenous), beneath the skin (subcutaneous), or into the spinal fluid (intrathecal) in their own homes. This treatment modality is an alternative to receiving such therapies in a hospital or other healthcare facility. It allows patients to receive medical care while maintaining their comfort and independence in a familiar environment. Home infusion therapy can be used for various conditions, including infections that require antibiotics or antifungals, pain management, hydration, chemotherapy, and other specialized infusions.
The process typically involves the placement of a catheter or needle, often with the help of a home healthcare nurse, who also provides training to the patient or their caregiver for self-administration. A pharmacist is responsible for preparing and compounding the medications, ensuring their sterility, stability, and accurate dosing. Home infusion therapy services may also include regular monitoring, assessment, and communication with the prescribing physician to manage the patient's treatment plan effectively.
Home infusion therapy has been shown to improve patient outcomes, increase satisfaction, and reduce healthcare costs compared to traditional inpatient care. It is a valuable option for patients who require ongoing therapies but prefer to recover or manage their conditions at home.
Akinetic mutism is a neurological condition characterized by a severe decrease in initiating and sustaining voluntary movements and speech, along with a decreased level of responsiveness to the environment. It is often caused by damage to the frontal lobe of the brain, particularly to the anterior cingulate cortex and its connections to other parts of the brain.
People with akinetic mutism may appear awake and have their eyes open, but they are generally unresponsive to external stimuli and do not initiate voluntary movements or speech on their own. They may occasionally respond to direct questions or commands, but their responses are often limited and delayed. The condition can be caused by various factors, including brain injury, stroke, tumors, infections, or degenerative diseases such as Parkinson's disease.
Akinetic mutism is distinct from a vegetative state, which is characterized by the absence of both awareness and sleep-wake cycles. In contrast, people with akinetic mutism may retain some degree of awareness and have sleep-wake cycles, although their level of responsiveness is significantly reduced.
Serotonin 5-HT2 receptor antagonists are a class of drugs that block the action of serotonin, a neurotransmitter, at 5-HT2 receptors. These receptors are found in the central and peripheral nervous systems and are involved in various physiological functions such as mood regulation, cognition, appetite control, and vasoconstriction.
By blocking the action of serotonin at these receptors, serotonin 5-HT2 receptor antagonists can produce a range of effects depending on the specific receptor subtype that they target. For example, some serotonin 5-HT2 receptor antagonists are used to treat psychiatric disorders such as schizophrenia and depression, while others are used to treat migraines or prevent nausea and vomiting associated with chemotherapy.
Some common examples of serotonin 5-HT2 receptor antagonists include risperidone, olanzapine, and paliperidone (used for the treatment of schizophrenia), mirtazapine (used for the treatment of depression), sumatriptan (used for the treatment of migraines), and ondansetron (used to prevent nausea and vomiting).
Serotonin 5-HT2 receptor agonists are a class of compounds that bind to and activate the serotonin 5-HT2 receptors, which are a type of G protein-coupled receptor found in the central and peripheral nervous systems. These receptors play important roles in various physiological processes, including neurotransmission, vasoconstriction, and smooth muscle contraction.
Serotonin 5-HT2 receptor agonists can produce a range of effects depending on the specific subtype of receptor they activate. For example, activation of 5-HT2A receptors has been associated with hallucinogenic effects, while activation of 5-HT2B receptors has been linked to cardiac valvulopathy.
These drugs are used in a variety of clinical settings, including the treatment of psychiatric disorders such as depression and schizophrenia, migraine headaches, and cluster headaches. Examples of serotonin 5-HT2 receptor agonists include LSD, psilocybin, ergotamine, and sumatriptan.
Dopamine D3 receptors are a type of G protein-coupled receptor that bind to the neurotransmitter dopamine. They are classified as part of the D2-like family of dopamine receptors, which also includes the D2 and D4 receptors. The D3 receptor is primarily expressed in the limbic areas of the brain, including the hippocampus and the nucleus accumbens, where it plays a role in regulating motivation, reward, and cognition.
D3 receptors have been found to be involved in several neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia, and drug addiction. In Parkinson's disease, the loss of dopamine-producing neurons in the substantia nigra results in a decrease in dopamine levels and an increase in D3 receptor expression. This increase in D3 receptor expression has been linked to the development of motor symptoms such as bradykinesia and rigidity.
In schizophrenia, antipsychotic medications that block D2-like receptors, including D3 receptors, are used to treat positive symptoms such as hallucinations and delusions. However, selective D3 receptor antagonists have also been shown to have potential therapeutic effects in treating negative symptoms of schizophrenia, such as apathy and anhedonia.
In drug addiction, D3 receptors have been found to play a role in the rewarding effects of drugs of abuse, such as cocaine and amphetamines. Selective D3 receptor antagonists have shown promise in reducing drug-seeking behavior and preventing relapse in animal models of addiction.
Overall, dopamine D3 receptors play an important role in several neurological and psychiatric disorders, and further research is needed to fully understand their functions and potential therapeutic uses.
Bromocriptine is a dopamine receptor agonist drug, which means it works by binding to and activating dopamine receptors in the brain. It has several therapeutic uses, including:
* Treatment of Parkinson's disease: Bromocriptine can be used alone or in combination with levodopa to help manage the symptoms of Parkinson's disease, such as stiffness, tremors, spasms, and poor muscle control.
* Suppression of lactation: Bromocriptine can be used to suppress milk production in women who are not breastfeeding or who have stopped breastfeeding but still have high levels of prolactin, a hormone that stimulates milk production.
* Treatment of pituitary tumors: Bromocriptine can be used to shrink certain types of pituitary tumors, such as prolactinomas, which are tumors that secrete excessive amounts of prolactin.
* Management of acromegaly: Bromocriptine can be used to manage the symptoms of acromegaly, a rare hormonal disorder characterized by abnormal growth and enlargement of body tissues, by reducing the production of growth hormone.
Bromocriptine is available in immediate-release and long-acting formulations, and it is usually taken orally. Common side effects of bromocriptine include nausea, dizziness, lightheadedness, and drowsiness. Serious side effects are rare but can include hallucinations, confusion, and priapism (prolonged erection).
Dopamine agonists are a class of medications that mimic the action of dopamine, a neurotransmitter in the brain that regulates movement, emotion, motivation, and reinforcement of rewarding behaviors. These medications bind to dopamine receptors in the brain and activate them, leading to an increase in dopaminergic activity.
Dopamine agonists are used primarily to treat Parkinson's disease, a neurological disorder characterized by motor symptoms such as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. By increasing dopaminergic activity in the brain, dopamine agonists can help alleviate some of these symptoms.
Examples of dopamine agonists include:
1. Pramipexole (Mirapex)
2. Ropinirole (Requip)
3. Rotigotine (Neupro)
4. Apomorphine (Apokyn)
Dopamine agonists may also be used off-label to treat other conditions, such as restless legs syndrome or certain types of dopamine-responsive dystonia. However, these medications can have significant side effects, including nausea, dizziness, orthostatic hypotension, compulsive behaviors (such as gambling, shopping, or sexual addiction), and hallucinations. Therefore, they should be used with caution and under the close supervision of a healthcare provider.
Serotonin receptor agonists are a class of medications that bind to and activate serotonin receptors in the body, mimicking the effects of the neurotransmitter serotonin. These drugs can have various effects depending on which specific serotonin receptors they act upon. Some serotonin receptor agonists are used to treat conditions such as migraines, cluster headaches, and Parkinson's disease, while others may be used to stimulate appetite or reduce anxiety. It is important to note that some serotonin receptor agonists can have serious side effects, particularly when taken in combination with other medications that affect serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs). This can lead to a condition called serotonin syndrome, which is characterized by symptoms such as agitation, confusion, rapid heart rate, high blood pressure, and muscle stiffness.
Antiparkinson agents are a class of medications used to treat the symptoms of Parkinson's disease and related disorders. These agents work by increasing the levels or activity of dopamine, a neurotransmitter in the brain that is responsible for regulating movement and coordination.
There are several types of antiparkinson agents, including:
1. Levodopa: This is the most effective treatment for Parkinson's disease. It is converted to dopamine in the brain and helps to replace the missing dopamine in people with Parkinson's.
2. Dopamine agonists: These medications mimic the effects of dopamine in the brain and can be used alone or in combination with levodopa. Examples include pramipexole, ropinirole, and rotigotine.
3. Monoamine oxidase B (MAO-B) inhibitors: These medications block the breakdown of dopamine in the brain and can help to increase its levels. Examples include selegiline and rasagiline.
4. Catechol-O-methyltransferase (COMT) inhibitors: These medications block the breakdown of levodopa in the body, allowing it to reach the brain in higher concentrations. Examples include entacapone and tolcapone.
5. Anticholinergic agents: These medications block the action of acetylcholine, another neurotransmitter that can contribute to tremors and muscle stiffness in Parkinson's disease. Examples include trihexyphenidyl and benztropine.
It is important to note that antiparkinson agents can have side effects, and their use should be carefully monitored by a healthcare professional. The choice of medication will depend on the individual patient's symptoms, age, overall health, and other factors.
Hallucinogens are a class of psychoactive substances that alter perception, mood, and thought, often causing hallucinations, which are profound distortions in a person's perceptions of reality. These substances work by disrupting the normal functioning of the brain, particularly the parts that regulate mood, sensory perception, sleep, hunger, and sexual behavior.
Hallucinogens can be found in various forms, including plants, mushrooms, and synthetic compounds. Some common examples of hallucinogens include LSD (d-lysergic acid diethylamide), psilocybin (found in certain species of mushrooms), DMT (dimethyltryptamine), and ayahuasca (a plant-based brew from South America).
The effects of hallucinogens can vary widely depending on the specific substance, the dose, the individual's personality, mood, and expectations, and the environment in which the drug is taken. These effects can range from pleasant sensory experiences and heightened emotional awareness to terrifying hallucinations and overwhelming feelings of anxiety or despair.
It's important to note that hallucinogens can be dangerous, particularly when taken in high doses or in combination with other substances. They can also cause long-term psychological distress and may trigger underlying mental health conditions. As such, they should only be used under the guidance of a trained medical professional for therapeutic purposes.
Serotonin antagonists are a class of drugs that block the action of serotonin, a neurotransmitter, at specific receptor sites in the brain and elsewhere in the body. They work by binding to the serotonin receptors without activating them, thereby preventing the natural serotonin from binding and transmitting signals.
Serotonin antagonists are used in the treatment of various conditions such as psychiatric disorders, migraines, and nausea and vomiting associated with cancer chemotherapy. They can have varying degrees of affinity for different types of serotonin receptors (e.g., 5-HT2A, 5-HT3, etc.), which contributes to their specific therapeutic effects and side effect profiles.
Examples of serotonin antagonists include ondansetron (used to treat nausea and vomiting), risperidone and olanzapine (used to treat psychiatric disorders), and methysergide (used to prevent migraines). It's important to note that these medications should be used under the supervision of a healthcare provider, as they can have potential risks and interactions with other drugs.