Levorphanol is an opioid analgesic that has been used in clinical practice for decades. It is a synthetic opioid derived from morphine and is structurally related to dihydromorphine. Levorphanol has strong analgesic properties with a long duration of action, making it suitable for the treatment of moderate to severe pain. It has also been used to treat certain types of coughs and is sometimes used in combination with other drugs to treat more severe cases.
The main pharmacological action of levorphanol is its agonist activity at the mu-opioid receptor. This receptor is one of the primary targets of opioids and is responsible for the analgesic and euphoric effects of these drugs. Levorphanol binds to the mu-opioid receptor with high affinity and also has agonist activity at the kappa-opioid receptor. The binding of levorphanol to the mu-opioid receptor results in the activation of G-protein coupled pathways and the subsequent release of several neurotransmitters, including dopamine. Levorphanol also has weak antagonist activity at the NMDA receptor, which likely contributes to its analgesic properties.
Levorphanol is rapidly absorbed following oral administration and has an elimination half-life of approximately 4 hours. It is metabolized mainly in the liver by N-dealkylation and glucuronidation. The metabolites of levorphanol are excreted primarily in the urine and to a lesser extent in the feces.
Levorphanol has a variety of adverse effects. The most common adverse effects include constipation, nausea, dizziness, and sedation. It can also cause respiratory depression, especially when combined with other CNS depressants such as alcohol. As with other opioids, levorphanol has the potential for addiction and abuse.
Levorphanol has an important role in the treatment of moderate to severe pain. Its long duration of action and its agonist activity at the mu-opioid receptor make it a useful and effective analgesic. However, its potential for addiction and abuse necessitate careful monitoring and proper usage.
References
Gomes-Leal, W., & Silva, M. A. (2020). Levorphanol. In StatPearls. Treasure Island (FL): StatPearls Publishing.
Kutlu, M. (2017). Levorphanol: An overview. International Journal of Pharmaceutical Sciences and Research, 8(7), 2531-2535.
Raffa, R. B., Friderichs, E., Reimann, W., & Shank, R. P. (1995). Opioid analgesics. In Goodman and Gilman’s The Pharmacological Basis of Therapeutics (pp. 341-363). McGraw-Hill Education.