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.^[2]

Butorphanol exhibits partial agonist and antagonist activity at the μ opioid receptor and agonist activity at the κ opioid receptor.^[2] 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.