Levorphanol
Encyclopedia
Levorphanol is an opioid
medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan
(Dromoran) and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic. Morphinan is the parent drug and prototype of a large series of opioid and/or NMDA antagonists and opioid agonists used in medicine including nalbuphine
, butorphanol
, dextromethorphan
, and others.
Levorphanol labeled with tritium
was used in the research which led to the discovery of opioid receptors in the human nervous system, including the first study published in 1971.
Levorphanol has the same properties as morphine
with respect to the potential for habituation
, tolerance, physical dependence
and withdrawal
syndrome. It is 4 to 8 times as potent as morphine and has a longer half-life. Approximately 30 mg of oral morphine is roughly equianalgesic
to 4 mg of oral levorphanol. The laevo isomer is the source of the narcotic properties of the racemic drug Dromoran, but the dextro isomers are also useful in medicine: in addition to acting on sigma receptors
, the O-methyl derivative of its dextrorotary isomer, dextromethorphan
, is a common NMDA receptor
antagonist and pro-drug to dextrorphan
. Oral doses of levorphanol come in 2 mg and 4 mg strengths or subcutaneous injection every 6 to 8 hours.
Levorphanol has affinity to μ, κ, and δ opioid receptor
s, but lacks complete cross-tolerance
with morphine
. 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 favourable of the strong narcotics. Its NMDA actions, similar to those of the phenylheptylamine open-chain narcotics such as methadone
and ketobemidone
, make levorphanol useful for types of pain that other analgesics may not be as effective against; levorphanol's sigma receptor, SNRI properties make it even more useful particularly for neuropathic pain.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan
Morphinan
Morphinan is the base chemical structure of a large chemical class of psychoactive drugs, consisting of opioid analgesics, cough suppressants, and dissociative hallucinogens, among others.- Chemical Derivatives :Immediate derivatives of morphinan include:...
(Dromoran) and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic. Morphinan is the parent drug and prototype of a large series of opioid and/or NMDA antagonists and opioid agonists used in medicine including nalbuphine
Nalbuphine
Nalbuphine is a semi-synthetic opioid used commercially as an analgesic under a variety of trade names, including Nubain. It is noteworthy in part for the fact that at low dosages, it is found much more effective by women than by men, and may even increase pain in men, leading to its...
, butorphanol
Butorphanol
Butorphanol is a morphinan-type synthetic opioid analgesic developed by Bristol-Myers. 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 most...
, dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
, and others.
Levorphanol labeled with tritium
Tritium
Tritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...
was used in the research which led to the discovery of opioid receptors in the human nervous system, including the first study published in 1971.
Levorphanol has the same properties as morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
with respect to the potential for habituation
Habituation
Habituation can be defined as a process or as a procedure. As a process it is defined as a decrease in an elicited behavior resulting from the repeated presentation of an eliciting stimulus...
, tolerance, physical dependence
Physical dependence
Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
and withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
syndrome. It is 4 to 8 times as potent as morphine and has a longer half-life. Approximately 30 mg of oral morphine is roughly equianalgesic
Equianalgesic
An equianalgesic chart is a conversion chart that lists equivalent doses ofanalgesics . Equianalgesic charts are used for calculation of an equivalent dose between different analgesics.-Format:Equianalgesic tables are available in different formats, such as pocket-sized cards for ease...
to 4 mg of oral levorphanol. The laevo isomer is the source of the narcotic properties of the racemic drug Dromoran, but the dextro isomers are also useful in medicine: in addition to acting on sigma receptors
Sigma-1 receptor
The sigma-1 receptor is a chaperone protein at the endoplasmatic reticulum that modulates calcium signaling through the IP3 receptor. In humans, the sigma-1 receptor is encoded by the SIGMAR1 gene....
, the O-methyl derivative of its dextrorotary isomer, dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
, is a common NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
antagonist and pro-drug to dextrorphan
Dextrorphan
Dextrorphan is a psychoactive drug of the morphinan chemical class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextro-stereoisomer of racemorphan, the levo-half being levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6...
. Oral doses of levorphanol come in 2 mg and 4 mg strengths or subcutaneous injection every 6 to 8 hours.
Levorphanol has affinity to μ, κ, and δ opioid receptor
Opioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
s, but lacks complete cross-tolerance
Cross-tolerance
Cross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to...
with morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
. 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 favourable of the strong narcotics. Its NMDA actions, similar to those of the phenylheptylamine open-chain narcotics such as methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
and ketobemidone
Ketobemidone
Ketobemidone is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted by it's metabolite norketobemidone. This makes it useful for some types of pain that don't respond well to other opioids...
, make levorphanol useful for types of pain that other analgesics may not be as effective against; levorphanol's sigma receptor, SNRI properties make it even more useful particularly for neuropathic pain.