Butorphanol

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Butorphanol
Butorphanol2DCSDT.svg
Butorphanol3DanJ.gif
Systematic (IUPAC) name
17-cyclobutylmethyl-morphinan-3,14-diol
Clinical data
Trade namesStadol
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa682667
Pregnancy cat.C/D (United States)
Legal statusControlled (S8) (AU) Schedule IV (US)
RoutesIV, intranasal, oral
Pharmacokinetic data
BioavailabilityNasal: 60-70%
MetabolismHepatic hydroxylated & glucuronidated
Half-life4-7 hours
ExcretionRenal, 75%
Biliary, 11-14%
Fecal, 15%
Identifiers
CAS number42408-82-2 N
ATC codeN02AX02 QR05DA90
PubChemCID 5361092
DrugBankDB00611
ChemSpider16735714 YesY
UNIIQV897JC36D YesY
KEGGD00837 N
ChEBICHEBI:3242 YesY
ChEMBLCHEMBL33986 YesY
Chemical data
FormulaC21H29NO2 
Mol. mass327.473 g/mol
 N (what is this?)  (verify)
 
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Butorphanol
Butorphanol2DCSDT.svg
Butorphanol3DanJ.gif
Systematic (IUPAC) name
17-cyclobutylmethyl-morphinan-3,14-diol
Clinical data
Trade namesStadol
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa682667
Pregnancy cat.C/D (United States)
Legal statusControlled (S8) (AU) Schedule IV (US)
RoutesIV, intranasal, oral
Pharmacokinetic data
BioavailabilityNasal: 60-70%
MetabolismHepatic hydroxylated & glucuronidated
Half-life4-7 hours
ExcretionRenal, 75%
Biliary, 11-14%
Fecal, 15%
Identifiers
CAS number42408-82-2 N
ATC codeN02AX02 QR05DA90
PubChemCID 5361092
DrugBankDB00611
ChemSpider16735714 YesY
UNIIQV897JC36D YesY
KEGGD00837 N
ChEBICHEBI:3242 YesY
ChEMBLCHEMBL33986 YesY
Chemical data
FormulaC21H29NO2 
Mol. mass327.473 g/mol
 N (what is this?)  (verify)

Butorphanol (AAN, BAN, INN and USAN) is a morphinan-type synthetic opioid analgesic developed by Bristol-Myers.[1] 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.

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[2]

Mechanism of action[edit]

Butorphanol exhibits partial agonist and antagonist activity at the μ opioid receptor, as well as competitive antagonist activity and partial agonist activity at the κ opioid receptor.[3] 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.

Place in therapy[edit]

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 more effective in reducing pain in women than in men.[3]

In veterinary use, butorphanol ("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 (Domitor)), benzodiazepines, or phenothiazines (acepromazine) in dogs, cats and exotic animals. It is frequently combined with xylazine or detomidine (Dormosedan etc.) in horses.[4]

Adverse effects[edit]

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.

Proprietary preparations[edit]

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.

Use in horses[edit]

Butorphanol is a commonly used narcotic for pain relief in horses. It is administered either IM or IV, with its analgestic 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, overdose, and precautions[edit]

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.

In addition to horses, butorphanol with or without acepromazine is frequently used in veterinary settings 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. The efficacy of opioids (as well as other drugs that slow down the system like anaesthetics) in treating reptiles is a question about which there is currently not a lot of data.

Notes[edit]

  1. ^ US Patent 3775414 - Process for the Preparation of 14-hydroxymorphinan Derivatives
  2. ^ http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html
  3. ^ 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. doi:10.1016/S0304-3959(99)00119-0. PMID 10534607. 
  4. ^ NOAH Compendium of Data Sheets for Animal Medicines 2005

References[edit]