Identification
- Summary
Pholcodine is an opioid antitussive used to suppress unproductive coughing.
- Generic Name
- Pholcodine
- DrugBank Accession Number
- DB09209
- Background
Pholcodine formula is 3-o-morpholinoethylmorphine and it is classified as an antitussive which is defined as an opioid cough suppressant. It belongs to the opioid family of compounds and it is widely used.1 Pholcodine activity is the suppression of unproductive cough and it also has a mild sedative effect with little or no analgesic effects.2 Pholcodine is not prescribed in the United States where it is classed as a Schedule I drug. It is categorized as Class B drug in the UK and officially taken out of the shelves in 2008. Pholcodine is not approved in Canada.
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Pholcodine (DB09209)
- Weight
- Average: 398.4953
Monoisotopic: 398.220557458 - Chemical Formula
- C23H30N2O4
- Synonyms
- folcodina
- Pholcodine
- External IDs
- IDS-NP-011(SECT.2)
Pharmacology
- Indication
Pholcodine is indicated as a cough suppressant for the temporary relief of non-productive dry cough. It is stated to present a required label indication of "temporary relief of dry cough."5 Cough is the respiratory movement that occurs after an irritation signal is transmitted to the central nervous system and further stimulates the medulla oblongata. This stimulation causes a motor output that is sent through motoneurons to the respiratory muscles. A non-productive cough is a type of cough characterized by the absence of sputum, and it has a large inspiration that will cause continuous coughing.
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- Contraindications & Blackbox Warnings
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The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine.6 It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action.7
- Mechanism of action
The mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the "cough center."7
Target Actions Organism AMu-type opioid receptor antagonistHumans AKappa-type opioid receptor antagonistHumans UDelta-type opioid receptor antagonistHumans - Absorption
After oral administration of 60 mg of pholcodine, the Tmax and Cmax are reported to be 1.3 hours and 26.3 ng/ml. In the same administration, the AUC in plasma and saliva are reported to be 1.67 and 6.61 mg h/l respectively. The absorption of pholcodine is reported to represent approximately 88% of the administered dose.1
- Volume of distribution
The reported volume of distribution depends on the pharmacokinetic model and it can be of 265L based on a one-compartment model to 3207L in a two-compartment model.4
- Protein binding
The protein binding of pholcodine is of approximately of 21-23% and it tends to have a slight variation depending if the administration is chronic.1
- Metabolism
The metabolism of pholcodine seems to be very slow4 and due to the elimination profile, it is thought that most of the administered dose undergoes metabolism. There is some evidence in preclinical trials that indicate that morphine is a minor metabolite of pholcodine and that it accounts for 1% of the administered dose.1
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- Route of elimination
After oral administration of pholcodine, the serum concentration peaks and declines in a monoexponential manner. The percent of the dose excreted unchanged is of approximately 25-30%. Part of the administered dose is composed by metabolites that can be recovered in urine. From the administered dose, the fecal excretion corresponds to the 5% of the administered dose as unchanged pholcodine.1
- Half-life
After oral administration of 60 mg of pholcodine, the half-life in plasma, saliva and urine are 45, 55 and 45 hours respectively.1
- Clearance
After oral administration of 60 mg of pholcodine, the clearance rate was reported to be 126 ml/min.1
- Adverse Effects
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Generally, pholcodine is significantly less toxic than codeine. Nonetheless, it is important to consider the significant depressive respiratory effect.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Pholcodine which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Pholcodine which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Pholcodine which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Pholcodine which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Pholcodine which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Pholcodine which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Pholcodine which could result in a higher serum level. Acrivastine Pholcodine may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Pholcodine which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Pholcodine which could result in a higher serum level. 
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- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image DHACODINE SYRUP 15 mg/5 ml Syrup 15 mg/5ml Oral DRUG HOUSES OF AUSTRALIA PTE. LTD. 1989-12-06 Not applicable Singapore 
DURO-TUSS FORTE COUGH LIQUID 45 mg/15 ml Elixir 45 mg/15mL Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 1993-01-18 Not applicable Singapore DURO-TUSS REGULAR COUGH LIQUID 15 mg/15 ml Elixir 15 mg/15ml Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 1993-01-18 Not applicable Singapore - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Difflam? Blackcurrant Sugar Free Cough Lozenges Pholcodine (5.5 mg) + Benzydamine hydrochloride (1.5 mg) + Cetylpyridinium chloride (1.33 mg) Lozenge Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 2009-01-22 Not applicable Singapore DURO-TUSS DECONGESTANT LINCTUS Pholcodine (15 mg/15ml) + Pseudoephedrine hydrochloride (60 mg/15ml) Elixir Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 1994-02-02 Not applicable Singapore Duro-Tuss Dry Cough Lozenges (Orange flavoured) Pholcodine (5.5 mg) + Cetylpyridinium chloride (1.33 mg) Lozenge Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 1999-01-21 Not applicable Singapore DURO-TUSS EXPECTORANT COUGH LIQUID Pholcodine (15 mg/15mL) + Bromhexine hydrochloride (12 mg/15mL) Elixir Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 1994-02-02 Not applicable Singapore Duro-Tuss? Lemon Dry Cough Lozenges Pholcodine (5.50 mg) + Cetylpyridinium chloride (1.33 mg) Lozenge Oral INOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED 2010-07-04 Not applicable Singapore PCE Syrup Pholcodine (10 mg/5ml) + Chlorpheniramine maleate (4 mg/5ml) Syrup Oral DUOPHARMA MANUFACTURING (BANGI) SDN BHD 2020-09-08 Not applicable Malaysia 
Categories
- ATC Codes
- R05DA08 — Pholcodine
- Drug Categories
- Alkaloids
- Analgesics
- Antitussive Agents
- Central Nervous System Agents
- Cough and Cold Preparations
- Drugs that are Mainly Renally Excreted
- Heterocyclic Compounds, Fused-Ring
- Morphinans
- Morphine Derivatives
- Opiate Alkaloids
- Opium Alkaloids and Derivatives
- Oxazines
- Peripheral Nervous System Agents
- Phenanthrenes
- Respiratory System Agents
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Morphinans
- Sub Class
- Not Available
- Direct Parent
- Morphinans
- Alternative Parents
- Phenanthrenes and derivatives / Tetralins / Coumarans / Aralkylamines / Alkyl aryl ethers / Piperidines / Morpholines / Trialkylamines / Secondary alcohols / Oxacyclic compounds show 4 more
- Substituents
- Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Coumaran / Dialkyl ether / Ether show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- morphinane alkaloid, organic heteropentacyclic compound (CHEBI:53579)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- LPP64AWZ7L
- CAS number
- 509-67-1
- InChI Key
- GPFAJKDEDBRFOS-FKQDBXSBSA-N
- InChI
- InChI=1S/C23H30N2O4/c1-24-7-6-23-16-3-4-18(26)22(23)29-21-19(5-2-15(20(21)23)14-17(16)24)28-13-10-25-8-11-27-12-9-25/h2-5,16-18,22,26H,6-14H2,1H3/t16-,17+,18-,22-,23-/m0/s1
- IUPAC Name
- (1S,5R,13R,14S,17R)-4-methyl-10-[2-(morpholin-4-yl)ethoxy]-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
- SMILES
- [H][C@@]12OC3=C(OCCN4CCOCC4)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O
References
- General References
- Chen ZR, Bochner F, Somogyi A: Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies. Br J Clin Pharmacol. 1988 Oct;26(4):445-53. [Article]
- Florvaag E, Johansson SG: The Pholcodine Case. Cough Medicines, IgE-Sensitization, and Anaphylaxis: A Devious Connection. World Allergy Organ J. 2012 Jul;5(7):73-8. doi: 10.1097/WOX.0b013e318261eccc. [Article]
- Murata A, Taniguchi Y, Hashimoto Y, Kaneko Y, Takasaki Y, Kudoh S: Discrimination of productive and non-productive cough by sound analysis. Intern Med. 1998 Sep;37(9):732-5. [Article]
- Findlay JW, Fowle AS, Butz RF, Jones EC, Weatherley BC, Welch RM, Posner J: Comparative disposition of codeine and pholcodine in man after single oral doses. Br J Clin Pharmacol. 1986 Jul;22(1):61-71. [Article]
- Australian government [Link]
- United Nations Office on Drugs and Crime [Link]
- WHO [Link]
- External Links
- Human Metabolome Database
- HMDB0041984
- KEGG Drug
- D07385
- PubChem Compound
- 5311356
- PubChem Substance
- 310265116
- ChemSpider
- 4470854
- 33431
- ChEBI
- 53579
- ChEMBL
- CHEMBL2105224
- ZINC
- ZINC000004217287
- Wikipedia
- Pholcodine
- MSDS
- Download (51.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count Not Available Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Syrup Oral 15 mg/5ml Lozenge Oral Lozenge Oral 1.5 mg Elixir Oral 15 mg/15ml Lozenge Oral 1.33 mg Elixir Oral 12 mg/15mL Solution Oral Elixir Oral 45 mg/15mL Elixir Oral 15 mg/15ml Liquid Oral Syrup Oral 5 mg/15ml Syrup Oral 5 mg/5ml Syrup Oral Liquid Oral Syrup Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 91ºC 'MSDS' boiling point (°C) 577.8ºC at 760 mmHg 'MSDS' water solubility Slightly soluble 'MSDS' logP 1.08 Molbase pKa 9.3 Moffat, 1986 - Predicted Properties
Property Value Source Water Solubility 0.489 mg/mL ALOGPS logP 1.09 ALOGPS logP 1.14 Chemaxon logS -2.9 ALOGPS pKa (Strongest Acidic) 13.78 Chemaxon pKa (Strongest Basic) 9.19 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 54.4 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 111.7 m3·mol-1 Chemaxon Polarizability 43.76 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- EMBL-EBI [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
References
- EMBL-EBI [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- EMBL-EBI [Link]
Drug created at October 20, 2015 19:39 / Updated at May 07, 2021 21:06