Butorphanol

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. 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, cats and horses due to low bioavailability in humans. Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. 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, cats and horses due to low bioavailability in humans. It was patented in 1971 and approved for medical use in 1979. 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. Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid receptor, as well as partial agonist activity at the κ-opioid receptor (Ki = 2.5 nM; EC50 = 57 nM; Emax = 57%). 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. 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. Butorphanol is the INN, USAN, BAN, and AAN, while torbugesic is the JAN. As the tartrate salt, butorphanol is known as butorphanol tartrate (USAN, BAN). 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 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. 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. Butorphanol was originally in Schedule II and at one point it was decontrolled.