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| Name | Buprenorphine | |||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00921 (APRD00670) | |||||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | |||||||||||||||||||||||||||||||||||||||||||||
| Groups | illicit, approved | |||||||||||||||||||||||||||||||||||||||||||||
| Description | A derivative of the opioid alkaloid thebaine that is a more potent 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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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Brand name mixtures | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 52485-79-7 | |||||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 467.6401 Monoisotopic: 467.303558805 |
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| Chemical Formula | C29H41NO4 | |||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=RMRJXGBAOAMLHD-IHFGGWKQSA-N | |||||||||||||||||||||||||||||||||||||||||||||
| InChI |
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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| 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[13.2.2.1^{2,8}.0^{1,6}.0^{6,14}.0^{7,12}]icosa-7,9,11-trien-11-ol
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| SMILES |
CO[C@]12CC[C@@]3(C[C@@H]1[C@](C)(O)C(C)(C)C)[C@H]1CC4=C5C(O[C@@H]2[C@@]35CCN1CC1CC1)=C(O)C=C4
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| Mass Spec | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Classes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Substructures | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Pharmacology | ||||||||||||||||||||||||||||||||||||||||||||||
| Indication | For the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence. | |||||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Buprenorphine is a synthetic opioid analgesic and thebaine derivative, with a longer duration of action than morphine. Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Buprenorphine may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. | |||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | 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. | |||||||||||||||||||||||||||||||||||||||||||||
| Absorption | 31% bioavailability (sublingual) | |||||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Protein binding | 96% | |||||||||||||||||||||||||||||||||||||||||||||
| 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, can further undergo glucuronidation.
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| Route of elimination | Buprenorphine, in common with morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. | |||||||||||||||||||||||||||||||||||||||||||||
| Half life | 37 hours | |||||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death. | |||||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
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| Properties | ||||||||||||||||||||||||||||||||||||||||||||||
| State | solid | |||||||||||||||||||||||||||||||||||||||||||||
| Melting point | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| General Reference |
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| AHFS Codes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| PDB Entries | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (344.9 KB) | |||||||||||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
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| Drug Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Food Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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Pharmacological action: yes
Actions: partial agonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin Organism class: humanUniProt ID: P35372 ![]() Gene: OPRM1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: yes
Actions: antagonist 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: humanUniProt ID: P41145 ![]() Gene: OPRK1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: unknown
Actions: antagonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins Organism class: humanUniProt ID: P41143 ![]() Gene: OPRD1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor
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![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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: P20815![]() Gene: CYP3A5 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol) UniProt ID: P10632![]() Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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: P24462![]() Gene: CYP3A7 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
6. UDP-glucuronosyltransferase 1-9 Actions: substrateUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols UniProt ID: O60656![]() Gene: UGT1A9 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate, inhibitor
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![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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: P33260![]() Gene: CYP2C18 ![]() Protein Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
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![]() Gene: CYP2C19 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase UniProt ID: P11509![]() Gene: CYP2A6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Transporters |
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1. Multidrug resistance protein 1 Actions: inhibitorEnergy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183![]() Gene: ABCB1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. ATP-binding cassette sub-family G member 2 Actions: inhibitorXenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123 UniProt ID: Q9UNQ0![]() Gene: ABCG2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Comments |
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This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.