Xorphanol ( INN) (developmental code name TR-5379 or TR-5379M), also known as xorphanol mesylate ( USAN), is an opioid

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

of the morphinan family that was never marketed. Xorphanol is a mixed

agonist–antagonist In pharmacology the term agonist-antagonist or mixed agonist/antagonist is used to refer to a drug which under some conditions behaves as an agonist (a substance that fully activates the receptor that it binds to) while under other conditions, beha ...

of opioid receptors, acting preferentially as a high-

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

partial agonist/near- full agonist of the κ-opioid receptor (K_i = 0.4 nM; EC₅₀ = 3.3 nM; = 49%; = 0.84) and to a lesser extent as a partial agonist of the μ-opioid receptor (K_i = 0.25 nM; IC₅₀ = 3.4 nM; = 29%) with lower relative intrinsic activity and marked

antagonistic An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

potential (including the ability to antagonize morphine-induced effects and induce opioid withdrawal in opioid-dependent individuals). The drug has also been found to act as an agonist of the

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligan ...

(K_i = 1.0 nM; IC₅₀ = 8 nM; = 76%). Xorphanol produces potent analgesia, and was originally claimed to possess a minimal potential for dependence or

abuse Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...

. Moreover, side effects in animal studies were relatively mild, with only

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

and nausea being prominent, although it also produced convulsions at the highest dose tested. However, human trials revealed additional side effects such as

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

s and

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

, and this was the subject of a lawsuit between the drug's inventors and the company to which they had licensed the marketing rights, which claimed that these side effects had not been revealed to them during the license negotiations.''Maruho Company Ltd v Miles Inc'' (1993) 13 F.3d 6
/ref> As a result of this dispute, the drug was never marketed commercially.

References

Analgesics Convulsants Delta-opioid receptor agonists Dissociative drugs Kappa-opioid receptor agonists Morphinans Phenols Semisynthetic opioids Cyclobutyl compounds {{analgesic-stub

See also

References