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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/09/03 07:10:05」(JST)

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Butorphanol (BC 2627) is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers.^[1]^[2]^[3] Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs and cats due to low bioavailability in humans.

Medical uses

The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor. Butorphanol is also quite effective at reducing post-operative shivering (owing to its Kappa agonist activity). Butorphanol is more effective in reducing pain in women than in men.^[4]

Pharmacology

Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid receptor, as well as partial agonist activity at the κ-opioid receptor (K_i = 2.5 nM; EC₅₀ = 57 nM; E_max = 57%).^[4]^[5] Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways. Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.^[6]

Side effects

As with other opioid analgesics, central nervous system effects (such as sedation, confusion, and dizziness) are considerations with butorphanol. Nausea and vomiting are common. Less common are the gastrointestinal effects of other opioids (mostly constipation). Another side effect experienced by people taking the medication is increased perspiration.

Society and culture

Name

Butorphanol is the INN, USAN, BAN, and AAN, while torbugesic is the JAN.^[1]^[2]^[3] As the tartrate salt, butorphanol is known as butorphanol tartrate (USAN, BANM).^[1]^[2]^[3]

Availability

Butorphanol is available in the U.S. as a generic drug; it is available in various nations under one of any number of trade names, including Moradol and Beforal (Brand name Stadol no longer available in the US); veterinary trade names include Butorphic, Dolorex, Morphasol, Torbugesic, and Torbutrol.

Legality

Butorphanol is listed under the Single Convention on Narcotic Drugs 1961 and in the United States is a Schedule IV Narcotic controlled substance with a DEA ACSCN of 9720; being in Schedule IV it is not subject to annual aggregate manufacturing quotas. The free base conversion ratio of the hydrochloride is 0.69.^[7] Butorphanol was originally in Schedule II and at one point it was decontrolled.

Veterinary use

In veterinary anesthesia, butorphanol (trade name: Torbugesic) is widely used as a sedative and analgesic in dogs, cats and horses. For sedation, it may be combined with tranquilizers such as alpha-2 agonists (medetomidine), benzodiazepines, or acepromazine in dogs, cats and exotic animals. It is frequently combined with xylazine or detomidine in horses.^[8]

Butorphanol is frequently used for post-operative and accident-related pain in small mammals such as dogs, cats, ferrets, coatis, raccoons, mongooses, various marsupials, some rodents and perhaps some larger birds, both in the operating suite and as a regular prescription medication for home use, for management of moderate to severe pain.

Although butorphanol is commonly used for pain relief in reptiles, no studies (as of 2014) have conclusively shown that is an effective analgesic in reptiles.^[9]

Use in horses

Butorphanol is a commonly used narcotic for pain relief in horses. It is administered either IM or IV, with its analgesic properties beginning to take effect about 15 minutes after injection and lasting 4 hours. It is also commonly paired with sedatives, such as xylazine and detomidine, to make the horse easier to handle during veterinary procedures.

Side effects specific to horses include sedation, CNS excitement (displayed by head pressing or tossing). Overdosing may result in seizures, falling, salivation, constipation, and muscle twitching. If an overdose occurs, a narcotic antagonist, such as naloxone, may be given. Caution should be used if butorphanol is administered in addition to other narcotics, sedatives, depressants, or antihistamines as it will cause an additive effect.

Butorphanol can cross the placenta, and it will be present in the milk of lactating mares who are given the drug.

The drug is also prohibited for use in competition by most equestrian organizations, including the FEI, which considers it a class A drug.

Notes

^ ^a ^b ^c J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 200–. ISBN 978-1-4757-2085-3.
^ ^a ^b ^c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 154–. ISBN 978-3-88763-075-1.
^ ^a ^b ^c I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 58–. ISBN 978-94-011-4439-1.
^ ^a ^b Gear, RW; Miaskowski C; Gordon NC; Paul SM; Heller PH; Levine JD (November 1999). "The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain". Pain. 83 (2): 339–45. PMID 10534607. doi:10.1016/S0304-3959(99)00119-0.
^ Gharagozlou, Parham; Hashemi, Ezzat; DeLorey, TimothyM; Clark, J David; Lameh, Jelveh (2006). "Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology. 6 (1): 3. ISSN 1471-2210. PMC 1403760 . PMID 16433932. doi:10.1186/1471-2210-6-3.
^ http://www.who.int/medicines/areas/quality_safety/4.1ButhorphanolCritReview.pdf
^ http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html
^ NOAH Compendium of Data Sheets for Animal Medicines 2005
^ Sladky, KK (2014). "Chapter 18: Analgesia". In Mader, DR; Divers, SJ. Current therapy in reptile medicine & surgery. Elsevier Health Sciences. pp. 217–229. ISBN 9780323242936.

References

Katzung, Bertam G. (Ed.) (2001) Basic & Clinical Pharmacology (8th ed.). New York: McGraw-Hill. ISBN 0-8385-0598-8.
DiPiro, Joseph T. et al. (2005) Pharmacotherapy: A Pathophysiologic Approach (6th ed.). New York: McGraw-Hill. ISBN 0-07-141613-7.
Stadol NS - monograph
Forney, Barbara C, MS, VMD. Equine Medications, Revised Edition.' Blood Horse Publications. Lexington. Kentucky. Copyright 2007.
The Merck Manual of Veterinary Medicine, 2004 edition (English)
The Merck Manual, 2004 Edition (German)
Mosby's Drug Guide 2004

UpToDate Contents

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English Journal

Propofol with ketamine following sedation with xylazine for routine induction of general anaesthesia in horses.

Posner LP, Kasten JI, Kata C.SourceDepartment of Molecular and Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
The Veterinary record.Vet Rec.2013 Nov 11. doi: 10.1136/vr.101906. [Epub ahead of print]
To document the suitability of intravenous propofol and ketamine following sedation with xylazine for routine anaesthetic induction in horses. Retrospective. 100 client-owned horses. Anaesthetic records were evaluated to determine: signalment, anaesthetic drug and dosages, need for additional induct
PMID 24218416

NOP Receptor Mediates Anti-analgesia Induced by Agonist-Antagonist Opioids.

Gear RW, Bogen O, Ferrari LF, Green PG, Levine JD.SourceDepartment of Oral and Maxillofacial Surgery, University of California, San Francisco, CA 94143-0440.
Neuroscience.Neuroscience.2013 Nov 1. pii: S0306-4522(13)00914-7. doi: 10.1016/j.neuroscience.2013.10.061. [Epub ahead of print]
Clinical studies have shown that agonist-antagonist opioid analgesics that produce their analgesic effect via action on the kappa-opioid receptor, produce a delayed-onset anti-analgesia in men but not women, an effect blocked by co-administration of a low dose of naloxone. We now report the same tim
PMID 24188792

A comparison in dogs of medetomidine, with or without MK-467, and the combination acepromazine-butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane.

Salla K, Bennett RC, Restitutti F, Junnila J, Raekallio M, Vainio O.SourceDepartment of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Veterinary anaesthesia and analgesia.Vet Anaesth Analg.2013 Oct 15. doi: 10.1111/vaa.12094. [Epub ahead of print]
OBJECTIVE: To compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.STUDY DESIGN: Prospective, randomized cross-over study.ANIMALS: Eight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.METHODS: The dogs were i
PMID 24127733

Japanese Journal

Anesthetic Effects of a Mixture of Medetomidine, Midazolam and Butorphanol in Two Strains of Mice

Kirihara Yumiko,Takechi Mayumi,Kurosaki Kaoru,Kobayashi Yuta,Kurosawa Tsutomu
Experimental Animals 62(3), 173-180, 2013
… butorphanol (But.) produced an anesthetic duration of around 40 min in outbred ICR mice. …
NAID 130003362954

Anesthetic and Cardiorespiratory Effects of Propofol, Medetomidine, Lidocaine and Butorphanol Total Intravenous Anesthesia in Horses

ISHIZUKA Tomohito,ITAMI Takaharu,TAMURA Jun,SAITOH Yasuo,SAITOH Motoaki,UMAR Mohammed A.,MIYOSHI Kenjirou,YAMASHITA Kazuto,MUIR William W.
Journal of Veterinary Medical Science 75(2), 165-172, 2013
… Anesthetic and cardiorespiratory effects of medetomidine, lidocaine, butorphanol and propofol total intravenous anesthesia (MLBP-TIVA) were evaluated in horses undergoing an experimental surgery. … Ten horses were premedicated with an intravenous injection (IV) of medetomidine (5 μg/kg) and butorphanol (20 μg/kg). …
NAID 130001879636

Intravenous butorphanol administration reduces intrathecal morphine-induced pruritus after cesarean delivery : a randomized, double-blind, placebo-controlled study

WU Zhen,KONG Mingjian,WANG Ning,FINLAYSON Roderick J.,DE TRAN Q. H.
Journal of anesthesia 26(5), 752-757, 2012-10-20
NAID 10031123500

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リンク元	「オピオイド」「ブトルファノール」
拡張検索	「butorphanol tartrate」

「オピオイド」

Butorphanol
Clinical data
Trade names	Stadol
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a682667
Pregnancy; category	C/D (United States);
Routes of; administration	IV, intranasal, oral
ATC code	N02AF01 (WHO) QR05DA90 (WHO);
Legal status
Legal status	AU: S8 (Controlled); CA: Schedule IV; US: Schedule IV;
Pharmacokinetic data
Bioavailability	Nasal: 60-70%
Metabolism	Hepatic hydroxylated & glucuronidated
Biological half-life	4-7 hours
Excretion	Renal, 75%; Biliary, 11-14%; Fecal, 15%
Identifiers
	IUPAC name (4bR, 8aR, 9S)-11-(cyclobutylmethyl)-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano) phenanthrene-3,8a-diol;
CAS Number	42408-82-2 ;
PubChem CID	5361092;
IUPHAR/BPS	7591;
DrugBank	DB00611 ;
ChemSpider	16735714 ;
UNII	QV897JC36D;
KEGG	D00837 ;
ChEBI	CHEBI:3242 ;
ChEMBL	CHEMBL33986 ;
ECHA InfoCard	100.050.717
Chemical and physical data
Formula	C21H29NO2
Molar mass	327.473 g/mol
3D model (JSmol)	Interactive image;
	SMILES OC1=CC2=C(C=C1)C[C@H]3N(CC[C@@]24CCCC[C@@]34O)CC5CCC5 ;
	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 ; Key:IFKLAQQSCNILHL-QHAWAJNXSA-N ;
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英: opioid
同: 類麻薬
関: オピオイド受容体

オピオイド受容体に結合するモルフィン様物質のことを指す。

内因性のオピオイドペプチドが発見され、これらは内因性オピオイドペプチドと呼ばれるようになった。

作用

縮瞳

モルフィンと多くのμ,κアゴニストは瞳孔の縮小を引き起こす。これは瞳孔を支配する副交感神経の興奮による。μアゴニストを中毒量投与すると縮瞳し、pinpoints pupupilsはpathognomonicである。(GOO.559)