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Fenfluramine
Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treatment of obesity, but was discontinued for this use due to cardiovascular toxicity before being repurposed for new indications. Fenfluramine was used for weight loss both alone under the brand name Pondimin and in combination with phentermine commonly known as fen-phen. Side effects of fenfluramine in people treated for seizures include decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, increased blood pressure, drooling, excessive salivation, fever, upper respiratory tract infection, vomiting, appetite loss, weight loss, falls, and status epilepticus. Fenfluramine acts as a serotonin and norepinephrin ...
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Fenfluramine/phentermine
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity medication that is no longer widely available. It was sold in the early 1990s, and utilized two anorectics. Fenfluramine was marketed by American Home Products (later known as Wyeth) as ''Pondimin'', but was shown to cause potentially fatal pulmonary hypertension and heart valve problems, which eventually led to its withdrawal in 1997 and legal damages of over $13 billion.Avorn J. (2004). ''Powerful Medicines'', pp. 71-84. Alfred A. Knopf. On the other hand, phentermine has side effects such as a fast heart beat, high blood pressure, trouble sleeping, dizziness, and restlessness. Fenfluramine acts as a serotonin releasing agent, phentermine as primarily a norepinephrine releasing agent. Phentermine also induces the release of serotonin and dopamine, although to a far lesser extent than it induces the release of norepinephrine. History Fenfluramine as a single drug was first introduc ...
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Phentermine
Phentermine, sold under the brand name Adipex-P among others, is a medication used together with diet and exercise to treat obesity. It is available by itself or as the combination phentermine/topiramate. Phentermine is taken by mouth. Common side effects include a fast heart beat, high blood pressure, trouble sleeping, dizziness, and restlessness. Serious side effects may include abuse, but do not include pulmonary hypertension or valvular heart disease, as the latter complications were caused by the fenfluramine component of the " fen-phen" combination. Phentermine is a norepinephrine and dopamine releasing agent (NDRA) and produces stimulant, rewarding, and appetite suppressant effects. Chemically, it is a substituted amphetamine. Phentermine was approved for medical use in the United States in 1959. It is available as a generic medication. In 2022, it was the 149th most commonly prescribed medication in the United States, with more than 3million prescriptions. Ph ...
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5-HT2B Receptor
5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the ''HTR2B'' gene. 5-HT2B is a member of the 5-HT2 receptor, 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, the 5-HT2B receptor is Gq protein, Gq/G11-protein coupled, leading to downstream activation of phospholipase C. Tissue distribution and function First discovered in the stomach of rats, 5-HT2B was challenging to characterize initially because of its structural similarity to the other 5-HT2 receptors, particularly 5-HT2C. The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system (CNS) effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of halluci ...
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Serotonin
Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, memory, and physiological processes such as vomiting and vasoconstriction. In the CNS, serotonin regulates mood, appetite, and sleep. Most of the body's serotonin—about 90%—is synthesized in the gastrointestinal tract by enterochromaffin cells, where it regulates intestinal movements. It is also produced in smaller amounts in the brainstem's raphe nuclei, the skin's Merkel cells, pulmonary neuroendocrine cells, and taste receptor cells of the tongue. Once secreted, serotonin is taken up by platelets in the blood, which release it during clotting to promote vasoconstriction and platelet aggregation. Around 8% of the body's serotonin is stored in platelets, and 1–2% is found in the CNS. Serotonin acts as both a vasoconstrictor and vas ...
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Serotonin–norepinephrine Releasing Agent
A serotonin–norepinephrine releasing agent (SNRA) is a type of drug which induces the release of serotonin and norepinephrine (and epinephrine) in the body and/or brain. Only a few SNRAs are known, examples of which include norfenfluramine, (''R'')-MDMA, MBDB, and MDAI. Fenfluramine produces norfenfluramine as a major active metabolite and hence is an SNRA similarly. It was formerly used as an appetite suppressant for the treatment of obesity. (''R'')-MDMA, MBDB, and MDAI are entactogens. A closely related type of drug is a serotonin–norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopaus ... (SNRI). Mechanism of action See also * Monoamine releasing agent * Serotonin releasing agent * Norepinephrine releasing agent * Serotonin–dopamine ...
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Appetite Suppressant
An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desire to eat. The understanding of anorexiant effects is crucial in the development of interventions for weight management, eating disorders, and related health concerns. The anorexiant effect can be induced through diverse mechanisms, ranging from hormonal regulation to neural signaling. Ghrelin, leptin, and peptide YY are among the hormones involved in appetite control. Additionally, neurotransmitters such as serotonin and dopamine in the central nervous system contribute significantly to the regulation of food intake. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Ancient Greek language, Greek and ), and such drugs are also known as anorexigenic, anorexiant, or appetite suppressant. History Us ...
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Dravet Syndrome
Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. It is very difficult to treat with anticonvulsant medications. It often begins before one year of age, with six months being the age that seizures, characterized by prolonged convulsions and triggered by fever, usually begin. Prolonged seizures in the first year of life are the most indicative physical manifestation of DS. DS is diagnosed clinically and genetic testing is recommended if there is any doubt. Due to drug-refractory epilepsy in DS, many other therapies are being explored to prolong the life expectancy of patients. Signs and symptoms Dravet syndrome has been characterized by prolonged febrile and non-febrile seizures within the first year of a child's life. This disease progresses to other seizure types like myoclo ...
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Combination Drug
A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fixed-dose combinations are mass production, mass-produced and mass marketing, mass marketed, intended to serve as a near universal treatment for a large patient population with diverse medical histories, conditions, predisposition thereof, and treatment requirements. A ''polypill'' is a tablet (pharmacy), pharmacy or capsule (pharmacy), capsule containing four or more active ingredients, often needing to be Compounding, compounded at a specialized pharmacy in order to satisfy the specifications of a patient's personalized medical prescription, prescription and treatment plan, including dosage form, Dosage (pharmacology), medicinal dosing, and/or modified-release dosage, mechanism of release. Polypills encompass approved drug, approved prescr ...
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5-HT2A Receptor
The 5-HT2A receptor is a subtype of the 5-HT2 receptor, 5-HT2 receptor that belongs to the serotonin receptor family and functions as a GPCR, G protein-coupled receptor (GPCR). It is a cell surface receptor that activates multiple intracellular signalling cascades. Like all 5-HT2 receptors, the 5-HT2A receptor is coupled to the Gq protein, Gq/G11 signaling pathway. It is the primary excitatory receptor subtype among the serotonin-responsive GPCRs. The 5-HT2A receptor was initially noted for its central role as the primary target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. It later regained research prominence when found to mediate, at least in part, the effects of many antipsychotic drugs, particularly atypical antipsychotic, atypical antipsychotics. Downregulation of post-synaptic 5-HT2A receptors is an adaptive response triggered by chronic administration of selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics. Elevated 5-HT2A ...
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5-HT2C Receptor
The 5-HT2C receptor is a subtype of the 5-HT2 receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a G protein-coupled receptor (GPCR) that is coupled to Gq/G11 and mediates excitatory neurotransmission. ''HTR2C'' denotes the human gene encoding for the receptor, that in humans is located on the X chromosome. As males have one copy of the gene and females have one of the two copies of the gene repressed, polymorphisms at this receptor can affect the two sexes to differing extent. Structure At the cell surface the receptor exists as a homodimer. The crystal structure has been known since 2018. Distribution 5-HT2C receptors are located mainly in the choroid plexus, and in rats is also found in many other brain regions in high concentrations, including parts of the hippocampus, anterior olfactory nucleus, substantia nigra, several brainstem nuclei, amygdala, subthalamic nucleus and lateral habenula. ...
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Decreased Appetite
Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others indicate a serious clinical condition or pose a significant risk. Anorexia is a symptom, not a diagnosis. The symptom also occurs in non-human animals, such as cats, dogs, cattle, goats, and sheep. In these species, anorexia may be referred to as inappetence. As in humans, loss of appetite can be due to a range of diseases and conditions, as well as environmental and psychological factors. Etymology The term is from (, 'without' + , spelled , meaning 'appetite'). Common manifestations Anorexia simply manifests as a decreased or loss of appetite. This can present as not feeling hungry or lacking the desire to eat. Sometimes people do not even notice they lack an appetite until they begin to lose weight from eating less. In oth ...
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