| Record Information |
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| Version | 2.0 |
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| Creation Date | 2009-07-21 20:27:58 UTC |
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| Update Date | 2014-12-24 20:25:53 UTC |
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| Accession Number | T3D2932 |
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| Identification |
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| Common Name | Buprenorphine |
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| Class | Small Molecule |
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| Description | Buprenorphine is a derivative of the opioid alkaloid thebaine that is a more potent (25 - 40 times) and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [PubChem] |
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| Compound Type | - Amine
- Analgesic, Opioid
- Drug
- Ether
- Metabolite
- Narcotic
- Narcotic Antagonist
- Organic Compound
- Synthetic Compound
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| Chemical Structure | |
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| Synonyms | | Synonym | | (-)-Buprenorphine | | (−)-buprenorphine | | 17-Cyclopropylmethyl-4,5alpha-epoxy-7alpha-((S)-1-hydroxy-1,2,2-trimethylpropyl)-6-methoxy-6,14-endo-ethanomorphinan-3-ol | | 2-(N-Cyclopropylmethyl-4,5alpha-epoxy-3-hydroxy-6-methoxy-6,14-endo-ethanomorphinan-6alpha-yl)-3,3-dimethyl-2-butanol | | 2-[3-Cyclopropylmethyl-11-hydroxy-15-methoxy-(14R)-13-oxa-3-azahexacyclo[13.2.2.12,8.01,6.06,14.07,12]icosa-7,9,11-trien-16-yl]-3,3-dimethyl-2-butanol | | 21-Cyclopropyl-7alpha-[(S)-1-hydroxy-1,2,2-trimethylpropyl]-6,14-endo-ethano-6,7,8,14-tetrahydrooripavine | | Addnok | | Buprel | | Buprenex | | Buprenophine | | Buprenorfina | | Buprenorphinum | | Buprigesic | | Butrans | | Morgesic | | Norphin | | Norspan | | Probuphine | | Subutex | | Temgesic | | Tidigesic |
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| Chemical Formula | C29H41NO4 |
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| Average Molecular Mass | 467.640 g/mol |
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| Monoisotopic Mass | 467.304 g/mol |
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| CAS Registry Number | 52485-79-7 |
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| IUPAC Name | (1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11-trien-11-ol |
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| Traditional Name | buprenorphine |
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| SMILES | [H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC3CC3)[C@]([H])(C4)[C@]11CC[C@@]2(OC)[C@]([H])(C1)[C@](C)(O)C(C)(C)C |
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| InChI Identifier | InChI=1S/C29H41NO4/c1-25(2,3)26(4,32)20-15-27-10-11-29(20,33-5)24-28(27)12-13-30(16-17-6-7-17)21(27)14-18-8-9-19(31)23(34-24)22(18)28/h8-9,17,20-21,24,31-32H,6-7,10-16H2,1-5H3/t20-,21-,24-,26+,27-,28+,29-/m1/s1 |
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| InChI Key | InChIKey=RMRJXGBAOAMLHD-IHFGGWKQSA-N |
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| Chemical Taxonomy |
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| Description | belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene. |
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| Kingdom | Organic compounds |
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| Super Class | Benzenoids |
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| Class | Phenanthrenes and derivatives |
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| Sub Class | Not Available |
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| Direct Parent | Phenanthrenes and derivatives |
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| Alternative Parents | |
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| Substituents | - Phenanthrene
- Azaspirodecane
- Tetralin
- Coumaran
- Alkyl aryl ether
- 1-hydroxy-2-unsubstituted benzenoid
- Aralkylamine
- Piperidine
- Tertiary alcohol
- Tertiary amine
- Tertiary aliphatic amine
- Dialkyl ether
- Ether
- Oxacycle
- Azacycle
- Organoheterocyclic compound
- Organooxygen compound
- Organonitrogen compound
- Organic nitrogen compound
- Alcohol
- Organopnictogen compound
- Hydrocarbon derivative
- Amine
- Organic oxygen compound
- Aromatic heteropolycyclic compound
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| Molecular Framework | Aromatic heteropolycyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Exogenous |
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| Cellular Locations | |
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| Biofluid Locations | Not Available |
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| Tissue Locations | Not Available |
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| Pathways | Not Available |
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| Applications | |
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| Biological Roles | |
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| Chemical Roles | Not Available |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | Not Available | | Boiling Point | Not Available | | Solubility | 1.68e-02 g/L | | LogP | 4.98 |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0a4i-9004200000-95c5673aa686eb387e74 | 2017-09-01 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive | splash10-05g4-9000120000-df9796e1ae0815a47d9b | 2017-10-06 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS ("Buprenorphine,1TMS,#1" TMS) - 70eV, Positive | Not Available | 2021-10-14 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-1000-3000900000-e02fba1e40b85e61b83c | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0a4i-9001400000-eed215cb420d242b3d55 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0a4i-9000000000-817bab94cec1acd1c7e8 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-014i-0001900000-285d935fade7fca577c3 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-014i-2005900000-d8e7f724df7328e6815e | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0ika-2009100000-36ff69a17a3778cc0036 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-014i-0000900000-6f5d221eee7743008b27 | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-014i-0000900000-58cbb866de1b4c36845e | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-014i-0000900000-c56569d00471b33e2382 | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-014i-0000900000-60c120f6e661a422e31f | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-014i-0000900000-60c120f6e661a422e31f | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-014i-0000900000-e4673887dac8f5daaf68 | 2021-10-11 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | 31% bioavailability (sublingual). Sublingual absorption is also dependent on pH. The length of time the tablet is under the tongue has little effect on absorption. Although buprenorphine is rapidly absorbed from the oral mucosa, the absorption into the systemic is slower. The time to reach peak plasma concentration (Tmax) varies between individuals (range of 40 minutes to 3.5 hours). How buprenorphine is formulated does not affect this pharmacokinetic parameter. It also undergoes extensive first-pass metabolism and as a consequence, has very low oral bioavailability. Coadministration with naloxone does not effect the pharmacokinetics of buprenorphine. |
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| Mechanism of Toxicity | Buprenorphine's analgesic effect is due to partial agonist activity at mu-opioid receptors. Buprenorphine is also a kappa-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. The binding to the mu and kappa receptors results in hyperpolarization and reduced neuronal excitability. Furthermore, buprenorphine slowly dissociates from its receptor. This observation would account for the longer duration of action compared to morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence. Its receptor fixation half life is 40 minutes which is significantly longer than morphine (milliseconds). |
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| Metabolism | Hepatic. Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation. The N-dealkylation pathway is mediated by cytochrome P-450 3A4 isozyme. Norbuprenorphine, an active metabolite and has one-fifth of the pharmacologic activity of the parent compound, can further undergo glucuronidation.
Route of Elimination: Buprenorphine, like morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. It is primarily eliminated via feces (as free forms of buprenorphine and norbuprenorphine) while 10 - 30% of the dose is excreted in urine (as conjugated forms of buprenorphine and norbuprenorphine).
Half Life: IV administration, 0.3 mg = 1.2 - 7.2 hours (mean 2.2 hours);
Sublingual administration = 37 hours. |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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| Uses/Sources | For the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence. |
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| Minimum Risk Level | Not Available |
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| Health Effects | Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. |
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| Symptoms | Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death. |
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| Treatment | The respiratory and cardiac status of the patient should be monitored carefully. In the event of depression of respiratory or cardiac function, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may not be effective in reversing any respiratory depression produced by buprenorphine. High doses of naloxone hydrochloride, 10-35 mg/70 kg may be of limited value in the management of buprenorphine overdose. Doxapram (a respiratory stimulant) also has been used. (6) |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | DB00921 |
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| HMDB ID | HMDB15057 |
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| PubChem Compound ID | 40400 |
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| ChEMBL ID | CHEMBL1201894 |
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| ChemSpider ID | 559124 |
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| KEGG ID | C08007 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 3216 |
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| BioCyc ID | Not Available |
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| CTD ID | Not Available |
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| Stitch ID | Buprenorphine |
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| PDB ID | Not Available |
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| ACToR ID | Not Available |
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| Wikipedia Link | Buprenorphine |
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| References |
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| Synthesis Reference | Kazuhisa Ninomiya, Yasuhiro Fukushima, Mutsuo Okumura, Yuko Hosokawa, “Buprenorphine percutaneous absorption preparation.” U.S. Patent US6090405, issued August, 1992. |
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| MSDS | Link |
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| General References | - Huang P, Kehner GB, Cowan A, Liu-Chen LY: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther. 2001 May;297(2):688-95. [11303059 ]
- Bodkin JA, Zornberg GL, Lukas SE, Cole JO: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. [7714228 ]
- Elkader A, Sproule B: Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005;44(7):661-80. [15966752 ]
- FDA label
- Drugs.com [Link]
- RxList: The Internet Drug Index (2009). [Link]
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| Gene Regulation |
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| Up-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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| Down-Regulated Genes | | Gene | Gene Symbol | Gene ID | Interaction | Chromosome | Details |
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