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Identification
Name Meperidine
Accession Number DB00454 (APRD00074)
Type small molecule
Groups approved
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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Centralgin
Demarol
Demerol
Dispadol
Dolantin
Dolcontral
Dolosal
Dolsin
Isonipecaine
Lidol
Lydol
Meperidine Hcl
Meperidol
Methyl phenylpiperidine carbonic acid ethyl ester
Nemerol
Operidine
Petantin
Pethanol
Pethidin
Pethidine
Pethidineter
Petydyna
Phetidine
Piperosal
Pipersal
Piridosal
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Brand mixtures Not Available
Categories
  • Narcotics
  • Analgesics
  • Adjuvants, Anesthesia
  • Opiate Agonists
  • Analgesics, Opioid
  • Adjuvants
CAS number 57-42-1
Weight Average: 247.3327
Monoisotopic: 247.157228921
Chemical Formula C15H21NO2
InChI Key InChIKey=XADCESSVHJOZHK-UHFFFAOYSA-N
InChI
InChI=1S/C15H21NO2/c1-3-18-14(17)15(9-11-16(2)12-10-15)13-7-5-4-6-8-13/h4-8H,3,9-12H2,1-2H3
Plain Text
IUPAC Name
ethyl 1-methyl-4-phenylpiperidine-4-carboxylate
SMILES
CCOC(=O)C1(CCN(C)CC1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
Substructures
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Acetates
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Phenylpropylamines
  • Piperidines
Pharmacology
Indication Used to control moderate to severe pain.
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.
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.
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.
Volume of distribution

Meperidine crosses the placenta and is distributed into breast milk.
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.
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.
Route of 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.
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.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Sanofi aventis us llc
  • Abbott laboratories pharmaceutical products div
  • Astrazeneca lp
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Elkins sinn div ah robins co inc
  • International medication systems ltd
  • Parke davis div warner lambert co
  • Watson laboratories inc
  • International medication system
  • Mallinckrodt chemical inc
  • Roxane laboratories inc
  • Barr laboratories inc
  • Caraco pharmaceutical laboratories ltd
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Mallinckrodt inc
  • Mikah pharma llc
  • Mikart inc
  • Mutual pharmaceutical co inc
  • Vintage pharmaceuticals inc
  • Wyeth ayerst laboratories
Packagers
Dosage forms
Form Route Strength
Solution Intravenous 10 mg/ml
Solution Oral 50 mg/5ml
Solution Parenteral 25 mg/ml, 50 mg/ml, 75 mg/ml, 100 mg/ml
Tablet Oral 50 mg, 100 mg
Prices
Unit description Cost Unit
Meperidine HCl 100 mg/ml vial 33.99 USD vial
Meperidine hcl powder 10.51 USD g
Demerol 100 mg tablet 3.33 USD tablet
Demerol 100 mg/ml vial 1.79 USD ml
Demerol 50 mg tablet 1.71 USD tablet
Meperidine HCl 100 mg tablet 1.33 USD tablet
Meperidine 100 mg tablet 1.31 USD tablet
Demerol 100 mg/ml ampul 1.1 USD ml
Meperidine Hydrochloride 100 mg/ml 1.1 USD ml
Meperidine Hydrochloride 75 mg/ml 1.04 USD ml
Meperidine Hydrochloride 50 mg/ml 0.98 USD ml
Meperidine HCl 50 mg tablet 0.93 USD tablet
Demerol 50 mg/ml vial 0.85 USD ml
Meperidine 10 mg/ml syringe 0.85 USD ml
Meperidine 50 mg tablet 0.69 USD tablet
Demerol 50 mg/ml ampul 0.58 USD ml
Meperidine 10 mg/ml cartrdge 0.3 USD ml
Demerol 50 mg Tablet 0.16 USD tablet
Meperidine HCl 50 mg/5ml Solution 0.14 USD ml
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 270 °C PhysProp
water solubility 3220 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 2.72 SANGSTER (1994)
logS -1.89 ADME Research, USCD
pKa 8.59 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 1.11e+00 g/l ALOGPS
logP 2.9 ALOGPS
logP 2.46 ChemAxon
logS -2.4 ALOGPS
pKa (strongest basic) 8.16 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 29.54 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 72.48 ChemAxon
polarizability 28.09 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07128 Link_out
PubChem Compound 4058 Link_out
PubChem Substance 46506899 Link_out
ChemSpider 3918 Link_out
BindingDB 50026752 Link_out
Therapeutic Targets Database DAP000230 Link_out
PharmGKB PA450369 Link_out
Drug Product Database 640409 Link_out
RxList http://www.rxlist.com/cgi/generic/meper.htm Link_out
Drugs.com http://www.drugs.com/cdi/meperidine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Meperidine Link_out
ATC Codes
  • N02AB02
AHFS Codes
  • 28:08.08
PDB Entries Not Available
FDA label show (173 KB)
MSDS show (6.6 KB)
Interactions
Drug Interactions
Drug Interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Chlorpromazine Increased sedation and hypotension
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil Possible antagonism of action
Eltrombopag Increases levels of Meperidine via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
Galantamine Possible antagonism of action
Isocarboxazid Potentially fatal adverse effects
Isoniazid Possible episodes of hypotension
Moclobemide Increased CNS toxicity (can cause death)
Phenelzine Potentially fatal adverse effects
Rasagiline Increased risk of serotonin syndrome. Concomitant use should be avoided.
Ritonavir Ritonavir increases the levels of analgesic
Rivastigmine Possible antagonism of action
Selegiline Potentially fatal adverse effects
Sibutramine Possible serotoninergic syndrome
Tipranavir Tipranavir may increase the adverse/toxic effects of Meperidine. Consider alternate therapy or monitor for Meperidine toxicity during concomitant use.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Concomitant use should be avoided.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Triprolidine The CNS depressants, Triprolidine and Meperidine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and meperidine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Food Interactions
  • Take without regard to meals. Avoid alcohol.
Targets

1. Kappa-type opioid receptor

Pharmacological action: yes

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out
Gene: OPRK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

2. Glutamate [NMDA] receptor subunit zeta-1

Pharmacological action: unknown
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors

Organism class: human
UniProt ID: Q05586 Link_out
Gene: GRIN1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Sakimura K, Shimoji K: N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg. 2000 Apr;90(4):928-32. Pubmed

3. Glutamate [NMDA] receptor subunit epsilon-2

Pharmacological action: unknown
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: Q13224 Link_out
Gene: GRIN2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Sakimura K, Shimoji K: N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg. 2000 Apr;90(4):928-32. Pubmed

4. Glutamate [NMDA] receptor subunit epsilon-1

Pharmacological action: unknown
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: Q12879 Link_out
Gene: GRIN2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Sakimura K, Shimoji K: N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg. 2000 Apr;90(4):928-32. Pubmed

5. Glutamate [NMDA] receptor subunit epsilon-3

Pharmacological action: unknown
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: Q14957 Link_out
Gene: GRIN2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Sakimura K, Shimoji K: N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg. 2000 Apr;90(4):928-32. Pubmed

6. Glutamate [NMDA] receptor subunit epsilon-4

Pharmacological action: unknown
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

Organism class: human
UniProt ID: O15399 Link_out
Gene: GRIN2D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamakura T, Sakimura K, Shimoji K: N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH. Anesth Analg. 2000 Apr;90(4):928-32. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos. 2004 Sep;32(9):930-6. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos. 2004 Sep;32(9):930-6. Pubmed

3. Cytochrome P450 2B6

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos. 2004 Sep;32(9):930-6. Pubmed

4. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ramirez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ: CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos. 2004 Sep;32(9):930-6. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Edwards DJ, Svensson CK, Visco JP, Lalka D: Clinical pharmacokinetics of pethidine: 1982. Clin Pharmacokinet. 1982 Sep-Oct;7(5):421-33. Pubmed

2. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Edwards DJ, Svensson CK, Visco JP, Lalka D: Clinical pharmacokinetics of pethidine: 1982. Clin Pharmacokinet. 1982 Sep-Oct;7(5):421-33. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19