molecular formula C18H21NO3 B1239579 Codeine monohydrate CAS No. 6059-47-8

Codeine monohydrate

カタログ番号: B1239579
CAS番号: 6059-47-8
分子量: 299.4 g/mol
InChIキー: OROGSEYTTFOCAN-DNJOTXNNSA-N
注意: 研究専用です。人間または獣医用ではありません。
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説明

コデインは、ケシPapaver somniferumの樹液に自然に存在するアルカロイドです。 コデインは、オピオイドであり、モルヒネのプロドラッグであり、主に痛み、咳、および下痢の治療に使用されます . コデインは、鎮痛、鎮咳、および制吐作用のために、医学において広く使用されています .

2. 製法

合成ルートと反応条件: この方法は、モルヒネとトリメチルフェニルアンモニウムクロリドを、アルカリ金属炭酸塩と炭化水素溶媒の存在下で、40°C〜120°Cの温度で反応させることを含みます .

工業生産方法: 工業的には、コデインは通常、アヘンから抽出されるか、モルヒネから合成されます。 抽出プロセスには、アヘンからモルヒネを分離し、メチル化によってコデインに変換することが含まれます .

反応の種類:

一般的な試薬と条件:

主要な生成物:

    酸化: コデノン。

    還元: ジヒドロコデイン。

    置換: ノルコデイン.

4. 科学研究における用途

コデインは、科学研究において、幅広い用途を持っています。

準備方法

Synthetic Routes and Reaction Conditions: This involves reacting morphine with trimethyl phenyl ammonium chloride in the presence of an alkali metal carbonate and a hydrocarbon solvent at temperatures ranging from 40°C to 120°C .

Industrial Production Methods: In industrial settings, codeine is often extracted from opium or synthesized from morphine. The extraction process involves isolating morphine from opium and then converting it to codeine through methylation .

Types of Reactions:

Common Reagents and Conditions:

Major Products:

    Oxidation: Codeinone.

    Reduction: Dihydrocodeine.

    Substitution: Norcodeine.

科学的研究の応用

Pharmacokinetics

Codeine is rapidly absorbed from the gastrointestinal tract, with less than 40% of an orally ingested dose reaching systemic circulation. The peak plasma concentration occurs within 1-2 hours, and its half-life ranges from 2.5 to 3.5 hours . Codeine's solubility and bioavailability are crucial for its effectiveness in various formulations.

Pain Management

Codeine is primarily indicated for the treatment of mild to moderate pain. It is often prescribed in combination with non-opioid analgesics like acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) for enhanced efficacy. Despite its common use, recent studies have raised questions about its effectiveness compared to other analgesics .

Cough Suppression

As an antitussive agent, codeine is effective in managing chronic cough associated with various etiologies. Its efficacy can vary based on underlying conditions, and alternatives such as dextromethorphan are sometimes preferred due to superior effectiveness .

Other Indications

  • Restless Leg Syndrome : Codeine may be beneficial for refractory cases of restless leg syndrome when other treatments fail.
  • Diarrhea : It is occasionally used in palliative care settings to manage persistent diarrhea .

Anticancer Potential

Recent studies have explored the potential anticancer properties of codeine. In vitro studies demonstrated that codeine can reduce cell viability in certain cancer cell lines, suggesting a possible role in cancer prevention or therapy. For instance, codeine showed significant growth inhibition in MCF-7 breast cancer cells and AGS gastric cancer cells when combined with other agents .

Antibacterial Activity

Research has also indicated that codeine complexes exhibit antimicrobial properties against various pathogens, suggesting potential applications beyond traditional uses .

Solubility Studies

Investigations into the solubility of codeine phosphate in supercritical carbon dioxide have been conducted to optimize drug delivery systems. Understanding solubility is essential for enhancing bioavailability and therapeutic effectiveness through micronization techniques .

Pain Management Case Study

A clinical trial involving patients with chronic pain evaluated the efficacy of codeine combined with acetaminophen versus acetaminophen alone. Results indicated that patients receiving the combination experienced greater pain relief without a significant increase in adverse effects.

Cough Management Case Study

A study on patients with chronic cough assessed the effectiveness of codeine syrup compared to dextromethorphan. Findings revealed that while both medications reduced cough frequency, dextromethorphan was preferred by patients due to fewer side effects and better overall satisfaction .

作用機序

コデインは、脳と脊髄のμ-オピオイド受容体に結合することで、効果を発揮します。 この結合は、侵害受容性神経伝達物質の放出を阻害し、鎮痛作用と痛みに対する耐性を高めます . コデインは、肝臓でシトクロムP450 2D6酵素によって代謝され、モルヒネを生成し、鎮痛作用をもたらします .

類似化合物:

コデインの独自性: コデインは、モルヒネやオキシコドンなどの他のオピオイドと比較して、比較的穏やかな効力と低い依存性リスクを持つ点が特徴です。 安全性の高いプロファイルのため、軽度から中等度の痛みや咳の治療に好まれることが多いです .

類似化合物との比較

Uniqueness of Codeine: Codeine is unique in its relatively mild potency and lower risk of addiction compared to other opioids like morphine and oxycodone. It is often preferred for treating mild to moderate pain and cough due to its favorable safety profile .

生物活性

Codeine monohydrate, a naturally occurring alkaloid derived from opium poppy, is primarily used for its analgesic and antitussive properties. Its biological activity is largely attributed to its interaction with the central nervous system through opioid receptors, particularly the mu-opioid receptor. This article delves into the pharmacodynamics, pharmacokinetics, metabolism, and clinical implications of this compound, supported by case studies and research findings.

Pharmacodynamics

Mechanism of Action
Codeine exerts its analgesic effects by binding to mu-opioid receptors in the brain and spinal cord, leading to a decrease in the perception of pain. It also interacts with kappa and delta opioid receptors, albeit to a lesser extent. This action results in hyperpolarization of nociceptive neurons, effectively impairing pain signal transmission .

Antitussive Activity
In addition to its analgesic properties, codeine is recognized for its antitussive effects. It suppresses cough reflexes by acting on the cough center in the medulla oblongata . Clinical trials have demonstrated its efficacy in treating cough associated with conditions such as tuberculosis .

Pharmacokinetics

Absorption and Bioavailability
Codeine is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within 1-2 hours post-administration. The bioavailability of codeine ranges from 30% to 40% due to extensive first-pass metabolism in the liver .

Metabolism
Approximately 70-80% of codeine is metabolized in the liver. Key metabolic pathways include:

  • O-Demethylation : Converts codeine into morphine (5-10%).
  • N-Demethylation : Produces norcodeine (10%).
  • Glucuronidation : Forms codeine-6-glucuronide (C6G), which is pharmacologically active .

The enzyme CYP2D6 plays a crucial role in converting codeine to morphine; genetic polymorphisms affecting CYP2D6 can lead to significant variability in individual responses to codeine .

Elimination
The elimination half-life of codeine ranges from 2.5 to 4 hours, with renal excretion being the primary route for its metabolites .

Distribution

Codeine is widely distributed throughout body tissues and can cross the blood-brain barrier as well as the placenta, which raises considerations for use during pregnancy and breastfeeding . The apparent volume of distribution is approximately 3-6 L/kg, indicating extensive tissue binding .

Clinical Implications

Case Studies

  • A case study highlighted myopathy and coordination issues linked to prolonged use of codeine linctus, suggesting potential adverse effects associated with chronic administration .
  • Another study discussed interactions between codeine and other medications (e.g., carbamazepine), emphasizing the importance of monitoring for adverse reactions when co-administered with other central nervous system depressants .

Summary Table of this compound Characteristics

CharacteristicDetails
Chemical Structure C18H21NO3 (with monohydrate form)
Mechanism of Action Mu-opioid receptor agonist
Bioavailability 30-40%
Peak Plasma Concentration 1-2 hours after oral administration
Half-Life 2.5 - 4 hours
Metabolites Morphine, norcodeine, C6G
Primary Metabolism Enzymes CYP2D6, UGT2B7, UGT2B4
Excretion Route Renal (urinary)

特性

CAS番号

6059-47-8

分子式

C18H21NO3

分子量

299.4 g/mol

IUPAC名

(4R,4aR,7S,7aR,12bS)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol

InChI

InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1

InChIキー

OROGSEYTTFOCAN-DNJOTXNNSA-N

SMILES

CN1CCC23C4C1CC5=C2C(=C(C=C5)OC)OC3C(C=C4)O.O

異性体SMILES

CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)OC)O[C@H]3[C@H](C=C4)O

正規SMILES

CN1CCC23C4C1CC5=C2C(=C(C=C5)OC)OC3C(C=C4)O

沸点

482 °F at 22 mmHg (sublimes) (NTP, 1992)
BP: 250 °C at 22 mm Hg

Color/Form

Orthorhombic crystals from water, dilute alcohol, ether
Colorless or white crystals or powde

密度

1.32 at 68 °F (NTP, 1992) - Denser than water;  will sink

引火点

167 °F (NTP, 1992)

melting_point

309 to 313 °F (after drying at 176 °F) (NTP, 1992)
154-156
157.5 °C

Key on ui other cas no.

6059-47-8

物理的記述

Codeine appears as colorless to white crystalline solid or white powder. Sublimes at 284 °F. Odorless. Bitter taste. pH (saturated aqueous solution) 9.8. (NTP, 1992)
Solid

ピクトグラム

Acute Toxic; Irritant; Health Hazard

関連するCAS

41444-62-6 (PO4)

溶解性

less than 1 mg/mL at 70 °F (NTP, 1992)
soluble in water
Soluble in water
Slightly soluble in water
Soluble in ethyl ether, benzene, chloroform, toluene;  very soluble in ethanol;  insoluble in petroleum ether
Soluble in alcohol and chloroform
0.577 g/L

同義語

Ardinex
Codeine
Codeine Phosphate
Isocodeine
N Methylmorphine
N-Methylmorphine

製品の起源

United States

Retrosynthesis Analysis

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Min. plausibility 0.01
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Top-N result to add to graph 6

Feasible Synthetic Routes

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Q & A

Q1: What structural information about codeine monohydrate, codeine (anhydrous), and dihydrocodeinone is available from the research paper?

A1: The research paper titled "UNIT CELL, SPACE GROUP, AND INDEXED X-RAY DIFFRACTION POWDER DATA FOR CERTAIN NARCOTICS: I. This compound, CODEINE (ANHYDROUS), DIHYDROCODEINONE" [] investigates the crystallographic properties of these compounds. This includes determining the unit cell parameters, space group, and indexed X-ray diffraction powder data. This information is crucial for understanding the arrangement of molecules within the crystal lattice, which can influence properties such as stability, solubility, and bioavailability.

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