Butorphanol, also known as Stadol, is a synthetic opioid agonist-antagonist. This drug is used to treat moderate to severe pain. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord but its mechanism of action is still unclear. It is believed to interact with an opiate receptor site in the CNS, probably in or associated with the limbic system of the brain. The opiate antagonistic effect may result from competitive inhibition, as well as it could be due to other mechanisms. Butorphanol is a mixed agonist-antagonist that exerts antagonistic or partially antagonistic effects at mu opiate receptor sites but is thought to exert its agonistic effects at the kappa and sigma opiate receptors. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death. It is administered as an intramuscular or intravenous injection or as a nasal spray. Butorphanol inhibits the exchange of GTP for GDP which is required to activate the G-protein complex. This prevents the Gi subunit of the mu opioid receptor from inhibiting adenylate cyclase, which can therefore continue to catalyze ATP into cAMP. cAMP increases the excitability in spinal cord pain transmission neurons which allows the patient to feel pain rather than the analgesic effects of opioids. The inhibition of Mu-type opioid receptors also prevents the Gi subunit of the mu opioid receptor from activating the inwardly rectifying potassium channel increasing K+ conductance which would cause hyperpolarization. Butorphanol also prevents the gamma subunit of the mu opioid receptor from inhibiting the N-type calcium channels on the neuron. This allows calcium to enter the neuron and depolarize. The inhibition of mu-opioid receptors prevents hyperpolarization in the neuron, allowing it to fire at a normal rate. The neuron is able to depolarize and the high concentration of calcium releases GABA into the synapse which binds to GABA receptors. GABA receptors inhibits dopamine cell firing in the pain transmission neurons. This prevents the analgesic and depressive effects of opioids, preventing opioid overdose. GABA also inhibits dopamine cell firing in the reward pathway which is the main cause of addiction to opioids and other drugs.

Butorphanol Opioid Antagonist Pathway References