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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Monday, October 17, 2011

A Tribute to L-Dromoran

Levorphanol is known by the chemical name (L)-3-hydroxy-N-Methylmorphinan, or its generic name Levo-Dromoran. L-Dromoran is a member of the morphinan family. It is a fully synthetic analogue of morphine - containing the structural characteristics essential for morphine-like action (i.e. the N-methyl & 3-HO) - but omitting a number of morphine's other features. Levorphanol is only one modification away from the bare bones morphinan structure (N-methylmorphinan, off of which its entire class is based); this modification being specifically, the addition of the phenolic hydroxyl, which is essential for morphine activity. Its closest morphine derived relative is actually desomorphine, which is slightly more potent than levorphanol itself, and differs only with the presence of an oxygen bridge (i.e. the root of the prefix epoxy, in 'epoxymorphinan'). This is the key difference which sets the morphinans apart from the classical morphine-codeine family.

Levorphanol was originally marketed as an alternative to morphine for severe pain, and was a succesful painkiller during its era (1950's thru 1970's), and was utilized in the original research which led to the discovery of opioid receptors in the 1970's. With the release of newer opioids to market, the increased use of methadone for pain, and the introduction of sustained release preparations of existing opioids; much attention was fixed upon the newer products, leading to a decrease in its popularity. Once the brand name was discontinued, levorphanol became (and has remained) relatively obscure up to present.

The drug is still available generically, currently as the oral form only. But while research has shifted toward atypical analgesics and more of a novel approach to pain, a narcotic with multiple modes of action is a prime candidate. Levorphanol has been around for a while, but many are rediscovering its value as a painkiller and euphoriant - this includes doctors, researchers, patients & users, even clandestine hobby chemists, who acknowledge the relatively practical/rudimentary nature of synthesis, for this class of synthetics.

One might speculate that L-Dromoran is superior to morphine in the following respects:

A low(er) capacity to induce tolerance

An enhanced action on descending inhibitory pathways

Its multi-modal synergystic properties

Actions against hyperalgesia

Its unique applicability to severe chronic pain including cancer-related and neuropathic pain.

Its long duration of action and accumulative phartmacokinetic properties; when dosed correctly this accumulation allows chronic doses to be reduced to as little as half the induction dose.

Often better tolerated than morphine, with less nausea & vomiting, pruritis, constipation, and very little to no clouding or sedation.

Its Pharmacodynamic Mechanisms of Action (A lower numerical value indicates a higher binding affinity for a particular site)

Very high affinity mu agonist - 0.21nM

High affinity kappa agonist - 2.3nM

Moderate affinity delta agonist - 4.2nM

High affinity NMDA antagonist - 0.6uM (methadone is 6.0uM, ketamine is 0.8uM)

5HT (i.e. serotonin) reuptake inhibitor

Norepinephrine reuptake inhibitor
 
For Some Good Literature on Levorphanol Tartrate:

1 comment:

  1. Great site, thanks. Levorphanol info isn't easy to come by. Your knowledge and efforts are greatly appreciated.

    ReplyDelete