(1S,9R,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.0^{1,10}.0^{2,7}]heptadeca-2(7),3,5-triene-4,10-diol

• ChemBase ID: 493
• Molecular Formular: C21H29NO2
• Molecular Mass: 327.46046
• Monoisotopic Mass: 327.21982917
• SMILES: O[C@@]12[C@]3(CCN([C@H]1Cc1c3cc(O)cc1)CC1CCC1)CCCC2
• Canonical SMILES: Oc1ccc2c(c1)[C@]13CCCC[C@]3([C@H](C2)N(CC1)CC1CCC1)O
• InChI: InChI=1S/C21H29NO2/c23-17-7-6-16-12-19-21(24)9-2-1-8-20(21,18(16)13-17)10-11-22(19)14-15-4-3-5-15/h6-7,13,15,19,23-24H,1-5,8-12,14H2/t19-,20+,21-/m1/s1
• InChIKey: IFKLAQQSCNILHL-QHAWAJNXSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,9R,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.0^{1,10}.0^{2,7}]heptadeca-2(7),3,5-triene-4,10-diol; (1S,9R,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.0^1,^1^0.0^2,^7]heptadeca-2(7),3,5-triene-4,10-diol
• IUPAC Traditional name: butorphanol
• Brand Name: Stadol; Moradol; Beforal; Stadol NS
• Synonyms: Butorfanol; Butorfanol [INN-Spanish]; Butorphanolum [INN-Latin]; Butorphanol Tartrate; Butorphanol; 17-(Cyclobutylmethyl)morphinan-3,14-diol; (-)-17-(Cyclobutylmethyl)-3,14β-dihydroxymorphinan; (-)-Butorphanol; BC 2627, (-)-; Butorphanol; Levo-BC 2627; l-3,14-Dihydroxy-N-(cyclobutylmethyl)morphinan; l-BC 2627; (-)-Butorphanol

Database IDs

• CAS Number: 58786-99-5; 42408-82-2
• PubChem SID: 160963956; 46507553
• PubChem CID: 6916249; 5361092

CALCULATED PROPERTIES

JChem

• LogD (pH = 5.5): 0.16574237
• LogD (pH = 7.4): 0.8131535
• Log P: 2.8903294
• Molar Refractivity: 95.921 cm^3
• Polarizability: 37.629734 Å^3
• Polar Surface Area: 43.7 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true
• Acid pKa: 9.864343
• H Acceptors: 3
• H Donor: 2

ALOGPS 2.1

• Log P: 3.65
• LOG S: -3.31
• Solubility (Water): 1.60e-01 g/l

PROPERTIES

Physical Property

• Solubility: Moderate
• Hydrophobicity(logP): 3.3

DETAILS

DrugBank - DB00611

• Drug Groups: illicit; approved
• Description: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [PubChem]
• Indication: For the relief of moderate to severe pain.
• Pharmacology: Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord.
• Toxicity: The clinical manifestations of butorphanol overdose are those of opioid drugs in general. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death.
• Affected Organisms: Humans and other mammals
• Biotransformation: Extensively metabolized in the liver. The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity.
• Absorption: Rapidly absorbed after intramuscular injection and peak plasma levels are reached in 20-40 minutes. The absolute bioavailability is 60-70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. Oral bioavailability is only 5-17% because of extensive first-pass metabolism.
• Half Life: The elimination half-life of butorphanol is about 18 hours. In renally impaired patients with creatinine clearances <30 mL/min the elimination half-life is approximately doubled. After intravenous administration to patients with hepatic impairment, the elimination half-life of butorphanol was approximately tripled.
• Protein Binding: Serum protein binding is approximately 80%.
• Elimination: Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion.
• Distribution: * 305 to 901 L
• Clearance: * 99 +/- 23 L/h [Young with IV 2 mg]; * 82 +/- 21 [Eldery with IV 2 mg]
• References: Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999 Nov;83(2):339-45. [Pubmed] ; Fan LW, Tanaka S, Tien LT, Ma T, Rockhold RW, Ho IK: Withdrawal from dependence upon butorphanol uniquely increases kappa(1)-opioid receptor binding in the rat brain. Brain Res Bull. 2002 Jun;58(2):149-60. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - B690550

Mixed opioid agonist-antagonist. Analgesic (narcotic); antitussive. Controlled substance.

REFERENCES

• Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999 Nov;83(2):339-45. Pubmed
• Fan LW, Tanaka S, Tien LT, Ma T, Rockhold RW, Ho IK: Withdrawal from dependence upon butorphanol uniquely increases kappa(1)-opioid receptor binding in the rat brain. Brain Res Bull. 2002 Jun;58(2):149-60. Pubmed
• Vargas-Arreola, F., et al.: Curr. Ther. Res., 22, 186 (1977)
• Heel, R.C., et al.: Drugs, 16, 473 (1977)