Butorphanol

Identification

Summary

Butorphanol is an opioid agonist-antagonist used to treat moderate to severe pain.

Brand Names
Stadol
Generic Name
Butorphanol
DrugBank Accession Number
DB00611
Background

A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain.

Type
Small Molecule
Groups
Approved, Illicit, Vet approved
Structure
Weight
Average: 327.4605
Monoisotopic: 327.219829177
Chemical Formula
C21H29NO2
Synonyms
  • (−)-17-(cyclobutylmethyl)morphinan-3,14-diol
  • (−)-butorphanol
  • (−)-N-cyclobutylmethyl-3,14-dihydroxymorphinan
  • Butorfanol
  • Butorphanol
  • Butorphanolum
External IDs
  • BC-2627
  • levo-BC 2627
  • LEVO-BC-2627

Pharmacology

Indication

For the relief of moderate to severe pain.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofPain•••••••••••••••••••••• •••••••••• ••••••••
Treatment ofPain, perioperative••••••••••••
Treatment ofSevere pain••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Mechanism of action

The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Butorphanol is believed to have both partial agonism and partial antagonism at the μ-opioid receptor, as well as partial agonist and antagonist activity at the κ-opioid receptor.

TargetActionsOrganism
AKappa-type opioid receptor
agonist
Humans
ADelta-type opioid receptor
agonist
Humans
AMu-type opioid receptor
antagonist
Humans
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.

Volume of distribution
  • 305 to 901 L
Protein binding

Serum protein binding is approximately 80%.

Metabolism

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.

Route of elimination

Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion.

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.

Clearance
  • 99 +/- 23 L/h [Young with IV 2 mg]
  • 82 +/- 21 [Eldery with IV 2 mg]
Adverse Effects
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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.

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.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Butorphanol is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of CNS depression can be increased when Butorphanol is combined with Acetazolamide.
AcetophenazineThe risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Butorphanol.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Butorphanol.
AgomelatineThe risk or severity of CNS depression can be increased when Butorphanol is combined with Agomelatine.
Food Interactions
  • Avoid alcohol.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Butorphanol tartrate2L7I72RUHN58786-99-5GMTYREVWZXJPLF-AFHUBHILSA-N
International/Other Brands
Butaro (Lotus Pharmaceuticals) / Butrum (Aristo)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
StadolInjection, solution1 mg/1mLIntramuscular; IntravenousE.R. Squibb & Sons, L.L.C.2004-01-012005-08-31US flag
StadolInjection, solution2 mg/1mLIntramuscular; IntravenousE.R. Squibb & Sons, L.L.C.1999-01-012000-01-01US flag
StadolInjection, solution2 mg/1mLIntramuscular; IntravenousE.R. Squibb & Sons, L.L.C.2004-01-012005-05-31US flag
StadolInjection, solution2 mg/1mLIntramuscular; IntravenousE.R. Squibb & Sons, L.L.C.2004-01-012005-08-31US flag
StadolInjection, solution2 mg/1mLIntramuscular; IntravenousPhysicians Total Care, Inc.1996-10-112011-05-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Butorphanol TartrateSpray10 mg/1mLNasalApotex Corp.2002-12-04Not applicableUS flag
Butorphanol TartrateInjection, solution2 mg/1mLIntramuscular; IntravenousHikma Pharmaceuticals USA Inc.2009-05-01Not applicableUS flag
Butorphanol TartrateInjection2 mg/1mLIntramuscular; IntravenousCardinal Health1998-10-152012-01-31US flag
Butorphanol TartrateInjection2 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals1998-10-152012-01-31US flag
Butorphanol TartrateInjection2 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals2008-05-052012-01-31US flag

Categories

ATC Codes
N02AF01 — Butorphanol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenanthrenes and derivatives
Sub Class
Not Available
Direct Parent
Phenanthrenes and derivatives
Alternative Parents
Benzazocines / Tetralins / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Tertiary alcohols / Trialkylamines / Cyclic alcohols and derivatives / 1,2-aminoalcohols / Azacyclic compounds
show 2 more
Substituents
1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzazocine / Cyclic alcohol / Hydrocarbon derivative
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
QV897JC36D
CAS number
42408-82-2
InChI Key
IFKLAQQSCNILHL-QHAWAJNXSA-N
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
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
SMILES
[H][C@@]12CC3=C(C=C(O)C=C3)[C@]3(CCCC[C@@]13O)CCN2CC1CCC1

References

Synthesis Reference

Monkovic, I. and Conway, T.T.; U.S. Patent 3,775,414; November 27,1973; Monkovic, I.,Wong, H. and Lim, G.; U.S. Patent 3,980,641; September 14, 1976; Pachter, IJ., Belleau, B.R. and Monkovic, I.; U.S. Patent 3,819,635; June 25,1974; and Lim, G. and Hooper, J.W.; U.S. Patent 4,017,497; April 12,1977; all assigned to Bristol-Myers Company.

General References
  1. 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. [Article]
  2. 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. [Article]
KEGG Drug
D00837
KEGG Compound
C06863
PubChem Compound
6916249
PubChem Substance
46507553
ChemSpider
16735714
BindingDB
50240437
RxNav
1841
ChEBI
3242
ChEMBL
CHEMBL33986
ZINC
ZINC000003812988
Therapeutic Targets Database
DAP000214
PharmGKB
PA164745398
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Butorphanol
FDA label
Download (320 KB)
MSDS
Download (60.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentColonoscopy1
4CompletedTreatmentCurettage / Pregnancy termination therapy1
4CompletedTreatmentHysterectomy / Postoperative pain1
4CompletedTreatmentPostoperative pain1
4Not Yet RecruitingTreatmentRespiratory Insufficiency1

Pharmacoeconomics

Manufacturers
  • Bedford laboratories div ben venue laboratories inc
  • Claris lifesciences ltd
  • Hikma farmaceutica (portugal) sa
  • Hikma farmaceutica sa
  • Hospira inc
  • Apothecon inc div bristol myers squibb
  • Mylan pharmaceuticals inc
  • Novex pharma
  • Roxane laboratories inc
  • Bristol myers squibb co pharmaceutical research institute
Packagers
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • Dispensing Solutions
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • Intervet International
  • Mead Johnson and Co.
  • Meridian Medical Technologies Inc.
  • Mylan
  • Novex Pharma
  • Patheon Inc.
  • Physicians Total Care Inc.
  • Roxane Labs
  • West-Ward Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionNasal10 mg / mL
InjectionIntramuscular; Intravenous1 mg/1mL
InjectionIntramuscular; Intravenous2 mg/1mL
PowderNot applicable1 mg/1mg
Spray, meteredNasal10 mg/1mL
SprayNasal10 mg / mL
Injection, solutionIntramuscular; Intravenous1 mg/1mL
Injection, solutionIntramuscular; Intravenous2 mg/1mL
SprayNasal10 mg/1mL
Aerosol, metered; liquidNasal10 mg / mL
Prices
Unit descriptionCostUnit
Butorphanol Tartrate 10 mg/ml Solution 2.5ml Bottle56.99USD bottle
Butorphanol 10 mg/ml spray39.63USD ml
Stadol 2 mg/ml vial10.11USD ml
Butorphanol 2 mg/ml vial7.2USD ml
Butorphanol 1 mg/ml vial3.6USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)272-274Monkovic, I. and Conway, T.T.; U.S. Patent 3,775,414; November 27,1973; Monkovic, I.,Wong, H. and Lim, G.; U.S. Patent 3,980,641; September 14, 1976; Pachter, IJ., Belleau, B.R. and Monkovic, I.; U.S. Patent 3,819,635; June 25,1974; and Lim, G. and Hooper, J.W.; U.S. Patent 4,017,497; April 12,1977; all assigned to Bristol-Myers Company.
water solubilityModerateNot Available
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.16 mg/mLALOGPS
logP3.65ALOGPS
logP2.89Chemaxon
logS-3.3ALOGPS
pKa (Strongest Acidic)9.86Chemaxon
pKa (Strongest Basic)10.7Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area43.7 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity95.92 m3·mol-1Chemaxon
Polarizability37.95 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9798
Blood Brain Barrier+0.9463
Caco-2 permeable+0.6844
P-glycoprotein substrateSubstrate0.8494
P-glycoprotein inhibitor IInhibitor0.5
P-glycoprotein inhibitor IIInhibitor0.5667
Renal organic cation transporterInhibitor0.6508
CYP450 2C9 substrateNon-substrate0.8248
CYP450 2D6 substrateSubstrate0.509
CYP450 3A4 substrateSubstrate0.5842
CYP450 1A2 substrateNon-inhibitor0.6532
CYP450 2C9 inhibitorNon-inhibitor0.9094
CYP450 2D6 inhibitorInhibitor0.6572
CYP450 2C19 inhibitorNon-inhibitor0.8456
CYP450 3A4 inhibitorNon-inhibitor0.8744
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9017
Ames testNon AMES toxic0.7587
CarcinogenicityNon-carcinogens0.9573
BiodegradationNot ready biodegradable0.9368
Rat acute toxicity2.6466 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5378
hERG inhibition (predictor II)Inhibitor0.5983
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-05c5-4090000000-ff08db00ae2474f6b4a5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-6318eb7086cc2b613e65
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-b422041d34eb1ba53942
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03fr-0029000000-829745194e66ba51af3c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-b422041d34eb1ba53942
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-004l-8296000000-760158b58d71322fa97a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0zor-0494000000-f61295de819439a89e25
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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
  1. Vivian JA, DeYoung MB, Sumpter TL, Traynor JR, Lewis JW, Woods JH: kappa-Opioid receptor effects of butorphanol in rhesus monkeys. J Pharmacol Exp Ther. 1999 Jul;290(1):259-65. [Article]
  2. Park Y, Jang CG, Ho IK, Ko KH: kappa-opioid agonist stimulated regional distribution of [(35)S]GTPgammas binding in butorphanol continuously infused rat. Brain Res Bull. 2000 May 1;52(1):17-20. [Article]
  3. 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. [Article]
  4. Fan LW, Tanaka S, Park Y, Sasaki K, Ma T, Tien LT, Rockhold RW, Ho IK: Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding. Brain Res. 2002 Dec 27;958(2):277-90. [Article]
  5. Commiskey S, Fan LW, Ho IK, Rockhold RW: Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16. Epub 2005 Jun 8. [Article]
  6. Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. [Article]
  7. Wakabayashi H, Tokuyama S, Ho IK: Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine. Neurochem Res. 1995 Oct;20(10):1179-85. [Article]
  8. Narita M, Feng Y, Makimura M, Hoskins B, Ho IK: Repeated administration of opioids alters characteristics of membrane-bound phorbol ester binding in rat brain. Eur J Pharmacol. 1994 Dec 27;271(2-3):547-50. [Article]
  9. Ohta S, Niwa M, Nozaki M, Tsurumi K, Shimonaka H, Tanahashi T, Uematsu H, Yamamoto M, Fujimura H: [Kappa-type opioid receptor in human placental membrane]. Masui. 1989 Oct;38(10):1293-300. [Article]
  10. Walsh SL, Chausmer AE, Strain EC, Bigelow GE: Evaluation of the mu and kappa opioid actions of butorphanol in humans through differential naltrexone blockade. Psychopharmacology (Berl). 2008 Jan;196(1):143-55. Epub 2007 Oct 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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
  1. 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. [Article]
  2. Fan LW, Tanaka S, Park Y, Sasaki K, Ma T, Tien LT, Rockhold RW, Ho IK: Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding. Brain Res. 2002 Dec 27;958(2):277-90. [Article]
  3. Commiskey S, Fan LW, Ho IK, Rockhold RW: Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16. Epub 2005 Jun 8. [Article]
  4. Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. [Article]
  5. Wakabayashi H, Tokuyama S, Ho IK: Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine. Neurochem Res. 1995 Oct;20(10):1179-85. [Article]
  6. Narita M, Feng Y, Makimura M, Hoskins B, Ho IK: Repeated administration of opioids alters characteristics of membrane-bound phorbol ester binding in rat brain. Eur J Pharmacol. 1994 Dec 27;271(2-3):547-50. [Article]
  7. Walsh SL, Chausmer AE, Strain EC, Bigelow GE: Evaluation of the mu and kappa opioid actions of butorphanol in humans through differential naltrexone blockade. Psychopharmacology (Berl). 2008 Jan;196(1):143-55. Epub 2007 Oct 2. [Article]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details
3. Mu-type opioid receptor
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
  1. Vivian JA, DeYoung MB, Sumpter TL, Traynor JR, Lewis JW, Woods JH: kappa-Opioid receptor effects of butorphanol in rhesus monkeys. J Pharmacol Exp Ther. 1999 Jul;290(1):259-65. [Article]
  2. 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. [Article]
  3. Fan LW, Tanaka S, Park Y, Sasaki K, Ma T, Tien LT, Rockhold RW, Ho IK: Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding. Brain Res. 2002 Dec 27;958(2):277-90. [Article]
  4. Commiskey S, Fan LW, Ho IK, Rockhold RW: Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16. Epub 2005 Jun 8. [Article]
  5. Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. [Article]
  6. Wakabayashi H, Tokuyama S, Ho IK: Simultaneous measurement of biogenic amines and their metabolites in rat brain regions after acute administration of and abrupt withdrawal from butorphanol or morphine. Neurochem Res. 1995 Oct;20(10):1179-85. [Article]
  7. Picker MJ: Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997 Dec;283(3):1009-17. [Article]
  8. Narita M, Feng Y, Makimura M, Hoskins B, Ho IK: Repeated administration of opioids alters characteristics of membrane-bound phorbol ester binding in rat brain. Eur J Pharmacol. 1994 Dec 27;271(2-3):547-50. [Article]
  9. Walsh SL, Chausmer AE, Strain EC, Bigelow GE: Evaluation of the mu and kappa opioid actions of butorphanol in humans through differential naltrexone blockade. Psychopharmacology (Berl). 2008 Jan;196(1):143-55. Epub 2007 Oct 2. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48