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    Pethidine molecular structure

    Pethidine Stats & Data

    Demerol Dolantin Meperidine Dolcontral
    NPS DataHub
    MW247.34
    FormulaC15H21NO2
    CAS57-42-1
    IUPACEthyl 1-methyl-4-phenylpiperidine-4-carboxylate
    SMILESCCOC(=O)C1(CCN(C)CC1)c1ccccc1
    InChIKeyXADCESSVHJOZHK-UHFFFAOYSA-N
    Chemical Class Opioid
    Psychoactive Class Depressant

    Pharmacology

    DrugBank
    State Solid

    Description

    A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.

    Mechanism of Action

    Meperidine is primarily a kappa-opiate receptor agonist and also has local anesthetic effects. Meperidine has more affinity for the kappa-receptor than morphine. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

    Pharmacodynamics

    Meperidine is a synthetic opiate agonist belonging to the phenylpiperidine class. Meperidine may produce less smooth muscle spasm, constipation, and depression of the cough reflex than equivalent doses of morphine. The onset of action is lightly more rapid than with morphine, and the duration of action is slightly shorter. The chemical structure of meperidine is similar to local anesthetics. Meperidine is recommended for relief of moderate to severe acute pain and has the unique ability to interrupt postoperative shivering and shaking chills induced by amphotericin B. Meperidine has also been used for intravenous regional anesthesia, peripheral nerve blocks and intraarticular, epidural and spinal analgesia. Meperidine is considered a second-line agent for the treatment of acute pain.

    Metabolism

    Meperidine is metabolized in the liver by hydrolysis to meperidinic acid followed by partial conjugation with glucuronic acid. Meperidine also undergoes N-demethylation to normeperidine, which then undergoes hydrolysis and partial conjugation. Normeperidine is about half as potent as meperidine, but it has twice the CNS stimulation effects.

    Absorption

    The oral bioavailability of meperidine in patients with normal hepatic function is 50-60% due to extensive first-pass metabolism. Bioavailability increases to 80-90% in patients with hepatic impairment (e.g. liver cirrhosis). Meperidine is less than half as effective when administered orally compared to parenteral administration. One study reported that 80-85% of the drug administered intramuscularly was absorbed within 6 hours of intragluteal injection in health adults; however, inter-individual variation and patient-specific variable appear to cause considerable variations in absorption upon IM injection.

    Indication

    Used to control moderate to severe pain.

    Half-life

    Initial distribution phase (t1/2 α) = 2-11 minutes; terminal elimination phase (t1/2 β) = 3-5 hours. In patients with hepatic dysfunction (e.g. liver cirrhosis or active viral hepatitis) the t1/2 β is prolonged to 7-11 hours.

    Protein Binding

    60-80% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. The presence of cirrhosis or active viral hepatitis does not appear to affect the extent of protein binding.

    Elimination

    Excreted in the urine. The proportion of drug that is excreted unchanged or as metabolites is dependent on pH. When urine pH is uncontrolled, 5-30% of the meperidine dose is excreted as normeperidine and approximately 5% is excreted unchanged. Meperidine and normeperidine are found in acidic urine, while the free and conjugated forms of meperidinic and normperidinic acids are found in alkaline urine.

    Volume of Distribution

    Meperidine crosses the placenta and is distributed into breast milk.

    Receptor Profile

    Receptor Actions

    Agonists
    μ-opioid receptor agonist (full)
    κ-opioid receptor agonist
    Antagonists
    Muscarinic acetylcholine receptor antagonist (M1/M2)
    Inhibitors
    Dopamine reuptake inhibitor
    Norepinephrine reuptake inhibitor (norpethidine metabolite is a serotonin reuptake inhibitor)

    Receptor Binding

    Kappa-type opioid receptor agonist
    Glutamate receptor ionotropic, NMDA 1 antagonist
    Glutamate receptor ionotropic, NMDA 2B antagonist
    Glutamate receptor ionotropic, NMDA 2A antagonist
    Glutamate receptor ionotropic, NMDA 2C antagonist
    Glutamate receptor ionotropic, NMDA 2D antagonist
    Mu-type opioid receptor agonist
    Sodium-dependent dopamine transporter inhibitor
    Sodium-dependent noradrenaline transporter inhibitor

    Effect Profile

    Curated + 19 Reports
    Opioid 7.6

    Strong euphoria and pain relief with moderate itching/nausea, mild sedation

    Euphoria / Warmth×3
    10
    Analgesia×2
    8
    Sedation / Relaxation×1
    4
    Itching / Nausea×1
    7

    Tolerance & Pharmacokinetics

    drugs.wiki

    Tolerance Decay

    Full tolerance 1d Half tolerance 21d Baseline ~35d

    Experience Report Analysis

    Erowid
    19 Reports
    2000–2019 Date Range
    6 With Age Data
    12 Effects Detected

    Demographics

    Gender Distribution

    Age Distribution

    Reports Over Time

    Effect Analysis

    Erowid

    Effects aggregated from 19 experience reports (19 Erowid)

    19 Reports
    12 Effects Detected
    8 Positive
    3 Adverse
    1 Neutral

    Effect Sentiment Distribution

    Confidence Distribution

    Positive Effects 8

    Euphoria 31.6% 70%
    Tactile Enhancement 26.3% 70%
    Sedation 26.3% 70%
    Stimulation 26.3% 70%
    Empathy 21.1% 70%
    Music Enhancement 21.1% 70%
    Pain Relief 15.8% 70%
    Focus Enhancement 15.8% 70%

    Adverse Effects 3

    Nausea 31.6% 70%
    Headache 21.1% 70%
    Confusion 21.1% 70%

    Real-World Dose Distribution

    62K Doses

    From 29 individual dose entries

    Oral (n=10)

    Median: 175.0mg 25th: 112.5mg 75th: 250.0mg 90th: 500.0mg
    mg/kg median: 1.84 mg/kg 75th: 3.617

    Insufflated (n=7)

    Median: 50.0mg 25th: 37.5mg 75th: 50.0mg 90th: 60.0mg
    mg/kg median: 0.648 mg/kg 75th: 0.748

    Form / Preparation

    Most common forms and preparations reported

    Body-Weight Dosing

    Dose relative to body weight from reports with weight data

    Median: 1.547 mg/kg IQR: 1.297–3.444 mg/kg n=5

    Redose Patterns

    Redosing behavior across 14 reports

    28.6% Redosed
    1.4 Avg Doses
    50m Median Interval

    Opioid Equivalence (MME)

    NIH HEAL 2024 & CDC 2022
    ⚠ Citation & Disclaimer: Conversion factors sourced from the NIH HEAL Initiative MME Calculator (Adams et al., PAIN 2025), the CDC 2022 Clinical Practice Guideline for Prescribing Opioids for Pain, and the MDCalc MME Calculator. These are approximate equianalgesic ratios for educational reference only. Individual responses vary significantly based on genetics, tolerance, cross-tolerance, and route of administration. This is not medical advice. Do not use these conversions to adjust opioid dosing without professional medical guidance.
    100 mg Pethidine 10 mg Morphine (oral)
    MME factor 0.1×

    Pethidine (meperidine) 100 mg oral ≈ 10 mg Morphine oral

    Also known as meperidine/Demerol. Neurotoxic metabolite normeperidine limits use. Evidence level: Moderate (B).

    Legal Status

    Country Status Notes
    Switzerland Pethidine is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
    Turkey Pethidine is a 'red prescription' only substance and illegal when sold or possessed without a prescription.
    United States Schedule II Caution : All legal information should be verified through other sources. see below U.S. FEDERAL LEGAL SUMMARY Meperidine - REGULATED: Yes - STATUS: Scheduled - SCHEDULE: Schedule II - CLASSIFICATION: Opiate Meperidine is Schedule II in the United States. This means it is illegal to sell without a DEA license and illegal to buy or possess without a license or prescription.
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