|Other names||Ro 1-5431|
|Main uses||Moderate to severe pain|
|Side effects||Nausea, flushing, urinary retention, itchiness, constipation, respiratory depression|
|Onset of action||With 1 hr|
|Duration of action||Up to 8 hrs|
|Typical dose||2 mg TID to QID|
|Bioavailability||70% (by mouth); 100% (IV)|
|Elimination half-life||11–16 hours|
|Chemical and physical data|
|Molar mass||257.377 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Levorphanol, sold under the brand name Levo-Dromoran, is an opioid medication used to treat moderate to severe pain. It is taken by mouth. Maximum effects occur within an hour and last up to 8 hours.
Common side effects include nausea, flushing, urinary retention, itchiness, and constipation. Other side effects may include insufficient breathing (respiratory depression), abuse, serotonin syndrome, and low blood pressure. Safety in pregnancy is unclear.
Levorphanol was first described in Germany in 1946. It has been in medical use in the United States since 1953. In the United States 90 tablets of 2 mg cost about 1,100 USD as of 2021. In the United States it is a Schedule II controlled substance.
It is generally started at 2 mg three to four times per day.
Levorphanol acts predominantly as an agonist of the μ-opioid receptor (MOR), but is also an agonist of the δ-opioid receptor (DOR), κ-opioid receptor (KOR), and the nociceptin receptor (NOP), as well as an NMDA receptor antagonist and a serotonin-norepinephrine reuptake inhibitor (SNRI). Levorphanol, similarly to certain other opioids, also acts as a glycine receptor antagonist and GABA receptor antagonist at very high concentrations. Levorphanol is 6 to 8 times as potent as morphine at the MOR.
Relative to morphine, levorphanol lacks complete cross-tolerance and possesses greater intrinsic activity at the MOR. The duration of action is generally long compared to other comparable analgesics and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favorable of the strong narcotics. Its antagonism of the NMDA receptor, similar to those of the phenylheptylamine open-chain opioids such as methadone or the phenylpiperidine ketobemidone, make levorphanol useful for types of pain that other analgesics may not be as effective against, such as neuropathic pain. Levorphanol's exceptionally high analgesic efficacy in the treatment of neuropathic pain is also conferred by its action on serotonin and norepinephrine transporters, similar to the opioids tramadol and tapentadol, and mutually complements the analgesic effect of its NMDA receptor antagonism.
Levorphanol shows a high rate of psychotomimetic side effects such as hallucinations and delirium, which have been attributed to its binding to and activation of the KOR. At the same time however, activation of this receptor as well as of the DOR have been determined to contribute to its analgesic effects.
Chemically, levorphanol belongs to the morphinan class and is (−)-3-hydroxy-N-methyl-morphinan. It is the "left-handed" (levorotatory) stereoisomer of racemorphan, the racemic mixture of the two stereoisomers with differing pharmacology. The "right-handed" (dextrorotatory) enantiomer of racemorphan is dextrorphan (DXO), an antitussive, potent dissociative hallucinogen (NMDA receptor antagonist), and weakly active opioid. DXO is an active metabolite of the pharmaceutical drug dextromethorphan (DXM), which, analogously to DXO, is an enantiomer of the racemic mixture racemethorphan along with levomethorphan, the latter of which has similar properties to those of levorphanol.
Society and culture
Levorphanol is the INN, BAN, and DCF. As the medically used tartrate salt, the drug is also known as levorphanol tartrate (USAN, BANM). The former developmental code name of levorphanol at Roche was Ro 1-5431.
Levorphanol is listed under the Single Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the U.S., it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9220 and 2013 annual aggregate manufacturing quota of 4.5 kilos. The salts in use are the tartrate (free base conversion ratio 0.58) and hydrobromide (0.76).
- Cough syrup
- Racemorphan; Dextrorphan;
- Codeine; Pholcodine
- Dextromethorphan; Dimemorfan
- Cloperastine; Levocloperastine
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