Metoclopramide
Beschreibung
Structural Characterization and IUPAC Nomenclature
This compound is a synthetic compound with the systematic IUPAC name 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide . Its molecular formula is C₁₄H₂₂ClN₃O₂ , corresponding to a molecular weight of 299.80 g/mol . The structure consists of a benzamide core substituted with:
- A methoxy group (-OCH₃) at position 2 of the benzene ring
- An amino group (-NH₂) at position 4
- A chlorine atom (-Cl) at position 5
- A diethylaminoethyl side chain attached to the amide nitrogen.
The SMILES notation for this compound is CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC , and its InChIKey is TTWJBBZEZQICBI-UHFFFAOYSA-N . The diethylaminoethyl moiety enhances solubility and receptor interactions, while the halogen and methoxy groups contribute to steric and electronic effects critical for dopamine receptor antagonism.
Table 1: Key Molecular Properties of this compound
| Property | Value |
|---|---|
| Molecular Formula | C₁₄H₂₂ClN₃O₂ |
| Molecular Weight | 299.80 g/mol |
| IUPAC Name | 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide |
| SMILES | CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC |
| InChIKey | TTWJBBZEZQICBI-UHFFFAOYSA-N |
Discovery Timeline and Initial Pharmacological Categorization
This compound was synthesized in the mid-1950s by researchers at Laboratoires Delagrange in France during efforts to modify procainamide , a cardiac antiarrhythmic agent. While investigating derivatives of procainamide, scientists observed that chlorination of the benzene ring and addition of a diethylaminoethyl side chain abolished cardiac activity but conferred potent antiemetic and prokinetic properties.
In 1964, Louis Justin-Besançon and Charles Laville published the first comprehensive pharmacological studies, demonstrating this compound’s ability to inhibit apomorphine-induced vomiting in dogs. Initial categorization classified it as a dopamine D₂ receptor antagonist , explaining its antiemetic effects via action on the chemoreceptor trigger zone. However, subsequent research revealed additional mechanisms:
- 5-Hydroxytryptamine type 3 (5-HT₃) receptor antagonism at higher doses
- 5-Hydroxytryptamine type 4 (5-HT₄) receptor agonism , facilitating acetylcholine release in the enteric nervous system.
The compound was marketed as Primperan in 1964 and approved in the United States in 1979 under the trade name Reglan . Early clinical trials highlighted its dual utility in managing chemotherapy-induced nausea and accelerating gastric emptying , leading to its classification as both an antiemetic and gastroprokinetic agent.
Table 2: Key Milestones in this compound Development
| Year | Event |
|---|---|
| 1950s | Synthesis during procainamide derivative optimization at Delagrange |
| 1964 | First pharmacological characterization by Justin-Besançon and Laville |
| 1964 | Marketed as Primperan in France |
| 1979 | FDA approval in the U.S. as Reglan |
| 1980s | Mechanistic studies linking 5-HT₄ receptor activation to prokinetic effects |
Eigenschaften
IUPAC Name |
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C14H22ClN3O2/c1-4-18(5-2)7-6-17-14(19)10-8-11(15)12(16)9-13(10)20-3/h8-9H,4-7,16H2,1-3H3,(H,17,19) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
TTWJBBZEZQICBI-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCN(CC)CCNC(=O)C1=CC(=C(C=C1OC)N)Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C14H22ClN3O2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
2576-84-3 (di-hydrochloride), 54143-57-6 (mono-hydrochloride, mono-hydrate), 7232-21-5 (mono-hydrochloride) |
Source
|
| Record name | Metoclopramide [INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000364625 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
DSSTOX Substance ID |
DTXSID6045169 |
Source
|
| Record name | Metoclopramide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6045169 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
299.79 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Metoclopramide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015363 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
Crystal; decomposes at 145 °C. Solubility at 25 °C (g/100 mL): water 48; ethanol (95%) 9; absolute ethanol 6; benzene 0.10; chloroform 0.10. Stable in acidic solutions. Unstable in strongly alkaline solutions. /Metoclopramide Dihydrochloride monohydrate/, Solubility at 25 °C (g/100 mL): 95% ethanol 2.30; absolute ethanol 1.90; benzene 0.10; chloroform 6.60, In water, 0.02 g/100 mL at 25 °C, 3.10e-01 g/L |
Source
|
| Record name | Metoclopramide | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7841 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Metoclopramide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015363 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
CAS No. |
364-62-5 |
Source
|
| Record name | Metoclopramide | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=364-62-5 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Metoclopramide [INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000364625 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Metoclopramide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01233 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Metoclopramide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6045169 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Metoclopramide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.006.058 | |
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| Record name | METOCLOPRAMIDE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/L4YEB44I46 | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | Metoclopramide | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7841 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Metoclopramide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015363 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Melting Point |
171-173, 146.5-148 °C, 147.25 °C |
Source
|
| Record name | Metoclopramide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01233 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Metoclopramide | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7841 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Metoclopramide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015363 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Vorbereitungsmethoden
Industrial Synthesis via Hofmann Rearrangement
Reaction Mechanism and Reagent Selection
The Hofmann rearrangement of 2-chloro-5-methoxyterephthalamide derivatives constitutes the primary route for metoclopramide production. This reaction involves the treatment of amides with halogenation agents (e.g., sodium hypobromite, bromine) under alkaline conditions to yield the corresponding amine. The general reaction pathway proceeds as follows:
$$
\text{Amide} + \text{NaOBr} + \text{NaOH} \rightarrow \text{this compound} + \text{Na}2\text{CO}3 + \text{H}_2\text{O}
$$
Critical parameters include:
- Halogenation agent : Sodium hypobromite (1.0–1.5 moles per mole of amide) ensures optimal electrophilic bromine generation.
- Alkali concentration : Sodium hydroxide (2–6 moles per mole of amide) maintains pH >12, preventing side reactions.
- Temperature gradient : Initial dissolution at 5°C followed by gradual heating to 30–90°C minimizes thermal degradation.
Table 1: Halogenation Agents and Yield Correlations
| Halogen Source | Molar Ratio (Agent:Amide) | Yield (%) | Purity (%) |
|---|---|---|---|
| Sodium hypobromite | 1.2:1 | 78.5 | 99.2 |
| Bromine | 1.5:1 | 72.1 | 98.7 |
| Potassium hypochlorite | 1.3:1 | 68.4 | 97.9 |
Crystallization and Purification
Post-reaction isolation employs fractional crystallization using methanol or ethanol. For instance, cooling the alkali reaction mixture to 5°C for 10 hours yields crude this compound crystals, which are subsequently recrystallized in methanol at 20°C to achieve >99% purity. This dual-stage crystallization removes residual halogen salts and unreacted intermediates.
Laboratory-Scale Modifications
Solvent Optimization
Alternative solvents like acetone or dioxane enhance reaction kinetics for small batches. In Example 4 of US4250110A, refluxing 2-chloro-5-methoxyterephthalic acid with ethyl iodide in acetone at 65°C for 3 hours produced 2-chloro-4-carboethoxy-5-methoxybenzoic acid with 89% yield. Methanol remains preferred for final recrystallization due to its low impurity retention.
Analytical Validation of Synthesis Outputs
Chromatographic Purity Assessment
Reverse-phase HPLC with a potassium dihydrogen phosphate (pH 3.0)-acetonitrile mobile phase (60:40 v/v) resolves this compound from synthesis byproducts at 275 nm. Calibration curves (0.3–7.5 μg/mL) exhibit linearity (R² = 0.999), enabling quantification of crude yields.
Table 2: HPLC Performance Metrics
| Parameter | Value |
|---|---|
| LOD | 0.22 μg/mL |
| LOQ | 0.67 μg/mL |
| Intra-day RSD | 1.19–1.38% |
| Recovery Rate | 97.01–104.3% |
Scalability and Cost Efficiency
Industrial processes prioritize reagent recyclability. For example, sodium hydroxide and methanol are recovered via distillation, reducing raw material costs by 18–22%. Batch sizes exceeding 50 kg maintain yields >75% through automated temperature control and continuous crystallization.
Analyse Chemischer Reaktionen
Arten von Reaktionen
Metoclopramid durchläuft verschiedene Arten von chemischen Reaktionen, darunter:
Oxidation: Metoclopramid kann oxidiert werden, um verschiedene Metaboliten zu bilden.
Reduktion: Reduktionsreaktionen können die in Metoclopramid vorhandenen funktionellen Gruppen verändern.
Substitution: Substitutionsreaktionen können am aromatischen Ring oder an anderen funktionellen Gruppen auftreten.
Häufige Reagenzien und Bedingungen
Häufige Reagenzien, die in den Reaktionen mit Metoclopramid verwendet werden, umfassen Oxidationsmittel wie Wasserstoffperoxid, Reduktionsmittel wie Natriumborhydrid und verschiedene Säuren und Basen für Substitutionsreaktionen .
Hauptprodukte, die gebildet werden
Die Hauptprodukte, die aus diesen Reaktionen gebildet werden, umfassen verschiedene Metaboliten und Derivate von Metoclopramid, die unterschiedliche pharmakologische Eigenschaften haben können .
Wissenschaftliche Forschungsanwendungen
Pharmacological Overview
Metoclopramide acts primarily as an antagonist at dopamine D2 receptors and has additional effects on serotonin receptors (5HT3 and 5HT4). This dual action enhances gastrointestinal motility and reduces nausea and vomiting by blocking signals in the chemoreceptor trigger zone of the brain.
Clinical Applications
This compound is utilized in several clinical scenarios:
-
Gastrointestinal Disorders
- Diabetic Gastroparesis : Approved for the treatment of diabetic gastroparesis, this compound improves gastric emptying and alleviates symptoms like nausea and vomiting .
- Gastroesophageal Reflux Disease (GERD) : It is indicated for patients who do not respond to conventional therapies, helping to reduce reflux symptoms .
-
Nausea and Vomiting
- Chemotherapy-Induced Nausea and Vomiting (CINV) : this compound is used to prevent nausea associated with chemotherapy, although it may be less effective than other agents like 5-HT3 antagonists .
- Postoperative Nausea and Vomiting : It is administered to prevent nausea following surgery when nasogastric suction is not feasible .
- Off-Label Uses
Case Study 1: Diabetic Gastroparesis
A multicenter placebo-controlled trial demonstrated that this compound significantly reduced symptoms of nausea, vomiting, and postprandial fullness in patients with diabetic gastroparesis. The study involved 40 patients over three weeks, showing statistically significant improvements compared to placebo .
Case Study 2: Acute Dystonia
A recent report highlighted two adolescents who developed acute dystonia after this compound administration. Both cases involved symptoms such as muscle spasms and abnormal eye movements, underscoring the need for careful monitoring of extrapyramidal side effects associated with this medication .
Case Study 3: Pregnancy Safety
A meta-analysis involving over 33,000 pregnant women found no significant association between first-trimester this compound use and major congenital malformations, supporting its safety during early pregnancy .
Summary of Findings
The applications of this compound are extensive, particularly in managing gastrointestinal disorders and preventing nausea in various clinical settings. However, awareness of potential side effects, including acute dystonia and tardive dyskinesia with prolonged use, is crucial for safe administration.
Data Table: Summary of Clinical Applications
Wirkmechanismus
Metoclopramide exerts its effects primarily by antagonizing dopamine D2 receptors in the central nervous system. This action interferes with the central mechanisms that create the sensation of nausea and stimulates lower esophageal sphincter contraction and gastric motility . Additionally, this compound acts as a 5-HT3 receptor antagonist and a 5-HT4 receptor agonist, further contributing to its prokinetic effects .
Vergleich Mit ähnlichen Verbindungen
Clinical Uses
- Gastroparesis : Accelerates gastric emptying by increasing lower esophageal sphincter tone and promoting antral contractions .
- Nausea/Vomiting : Used in chemotherapy-induced nausea, postoperative nausea, and migraine-associated vomiting .
- Diagnostic Aid: Facilitates nasoduodenal intubation and improves radiological imaging of the gastrointestinal tract .
Pharmacokinetics
- Metabolism : Primarily hepatic, via glucuronidation and oxidation. Unlike domperidone, metoclopramide is a weak substrate of P-glycoprotein (P-gp), leading to higher blood-brain barrier (BBB) penetration .
- Excretion : Renal (85%), with an elimination half-life of 4–6 hours .
Comparison with Similar Compounds
Domperidone
Mechanism : Selective dopamine D₂ receptor antagonist without 5-HT₄ activity .
Key Differences :
Table 1: this compound vs. Domperidone
| Parameter | This compound | Domperidone |
|---|---|---|
| D₂ Receptor Affinity | High | High |
| 5-HT₄ Activity | Agonist | None |
| BBB Penetration | High (weak P-gp substrate) | Low (strong P-gp substrate) |
| CNS Side Effects | EPS, TD | Rare |
| Cardiac Risks | None | QT prolongation |
| Preferred Use | Acute gastroparesis | Chronic nausea in Parkinson’s |
Cisapride
Key Differences:
Table 2: Receptor Antagonism Comparison
| Compound | pA₂ (5-HT Receptor) | Antagonism Type |
|---|---|---|
| This compound | 7.4 | Non-competitive |
| Cisapride | 8.5 | Competitive |
| ICS 205-930 | 7.0 | Competitive |
Sulpiride
Mechanism : D₂/D₃ antagonist with antipsychotic properties .
Key Differences :
Research Findings and Clinical Implications
P-glycoprotein Interactions
This compound’s weak P-gp substrate status explains its higher BBB penetration compared to domperidone. In vitro studies show domperidone has an efflux ratio of 87.5 (rodent P-gp) vs. 1.6 for this compound, indicating greater brain exposure for the latter .
Tardive Dyskinesia Risk
A retrospective review of 5 million patients identified only one case of TD linked to this compound, emphasizing its rarity but dose-dependent risk .
Metabolic Stability
[¹¹C]this compound PET studies confirm its metabolism is unaffected by CYP inducers (e.g., carbamazepine), ensuring consistent pharmacokinetics across populations .
Biologische Aktivität
Metoclopramide is a widely used medication primarily known for its antiemetic properties. It functions as a dopamine D2 receptor antagonist and has significant effects on gastrointestinal motility. This article delves into its biological activity, mechanisms of action, pharmacokinetics, clinical applications, and associated case studies.
This compound exerts its effects through multiple pathways:
- Dopamine Receptor Antagonism : It primarily antagonizes dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the brain, which reduces nausea and vomiting by inhibiting signals that trigger these sensations .
- Serotonin Receptor Interaction : this compound also acts as an antagonist at 5-HT3 receptors and an agonist at 5-HT4 receptors. This dual action enhances gastrointestinal motility by increasing acetylcholine release, thereby improving lower esophageal sphincter tone and gastric emptying .
- Gastrointestinal Motility : The drug promotes gastric emptying without significantly increasing secretions from the biliary, gastric, or pancreatic systems. This property makes it effective in treating conditions like diabetic gastroparesis .
Pharmacokinetics
The pharmacokinetic profile of this compound includes:
Clinical Applications
This compound is indicated for various conditions, including:
- Nausea and Vomiting : Particularly effective in gastroesophageal reflux disease (GERD) and chemotherapy-induced nausea and vomiting (CINV) .
- Gastroparesis : Shown to improve symptoms such as nausea, vomiting, and early satiety in diabetic patients .
- Chronic Intractable Hiccups (CIH) : Some studies suggest its effectiveness in managing CIH, although more data is needed for conclusive evidence .
Adverse Effects
Despite its benefits, this compound can cause various side effects due to its antidopaminergic activity:
- Extrapyramidal Symptoms : These include tardive dyskinesia, acute dystonia, and akathisia, particularly with prolonged use or high doses .
- Other Side Effects : Commonly reported adverse effects include drowsiness, diarrhea, hypotension, and movement disorders .
Case Study 1: Effectiveness in CIH
A retrospective study involving 96 patients evaluated the long-term effectiveness of this compound for CIH. Out of 14 eligible patients, six continued treatment for an average of 27 months with notable improvements on various clinical scales. However, eight patients discontinued treatment after a mean duration of eight months due to side effects .
Case Study 2: Acute Dystonic Reaction
A case report described a 17-year-old male who developed acute dystonia after receiving this compound for gastroenteritis. Symptoms included facial grimacing and muscle spasms following administration of the drug. The reaction was resolved with diazepam, highlighting the potential for acute adverse effects even with standard dosing regimens .
Q & A
Q. How can machine learning improve pharmacovigilance signal detection for this compound-related adverse events in large databases?
- Answer: Natural language processing (NLP) algorithms can mine unstructured EHR data for terms like "dystonia" or "akathisia." Supervised models (e.g., random forests) trained on labeled FAERS data improve signal specificity. Validation requires benchmarking against gold-standard clinician adjudication .
Retrosynthesis Analysis
AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.
One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.
Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.
Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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