|Summary sheet: Oxymorphazone|
|Common names||Oxymorphazone, oxymorphone hydrazone|
|Routes of Administration|
Oxymorphazone is a potent and long acting μ-opioid agonist synthesised in 1979 which binds irreversibly to the receptor, forming a covalent bond which prevents it from detaching once bound. This gives it an unusual pharmacological profile, and while oxymorphazone is only around half the potency of oxymorphone, with higher doses the analgesic effect becomes extremely long lasting, with a duration of up to 48 hours.
- 1 History and culture
- 2 Chemistry
- 3 Pharmacology
- 4 Subjective effects
- 5 Toxicity and harm potential
- 6 Legal status
- 7 See also
- 8 External links
- 9 References
History and culture
Oxymorphazone was first synthesised in 1979 by a team of Chemists at Rockefeller University, New York. Recent attempts to build effective irreversible opioid agonists encouraged the team to develop a hydrazone derivative of oxymorphone.
There is no documented human consumption of oxymorphazone. This is potentially due to its high addiction liability and extremely long duration.
Oxymorphazone is an opioid of the morphinan class. Oxymorphazone and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called phenanthrene. A fourth nitrogen containing ring is fused to the phenanthrene at R9 and R13 with the nitrogen member looking at R17 of the combined structure. This structure is called morphinan. Oxymorphazone is structurally similar to oxymorphone, with a C6 substitution of oxygen with a hydrazone group.
Oxymorphazone is long acting, irreversible μ-opioid receptor (MOR) agonist. This occurs due to the way in which opioids structurally mimic endogenous endorphins. Endorphins are responsible for analgesia (reducing pain), causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or excitement. This mimicking of natural endorphins results in the drug's euphoric, analgesic (pain relief), and anxiolytic (anti-anxiety) effects.
These appear to stem from the way in which opioids mimic endogenous endorphins. Endorphins are responsible for analgesia (reducing pain), causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or excitement. This mimicking of natural endorphins results in the drug's effects.
Oxymorphazone is estimated to be 50-100% as potent as oxymorphone. Although oxymorphazone is active on its own, research suggests that oxymorphazone's extremely long duration of effects and irreversible binding is a result of rapid degradation to oxymorphonazine. Oxymorphonazine is some 20-40x more potent and forms a covalent bond with the MOR, causing extensively long clearance.
Due to strong binding affinity and its long action, tolerance to oxymorphazone builds very rapidly and physical dependence is guaranteed, even from just one administration of the substance.
Disclaimer: The effects listed below are cited from the subjective effect index, which is based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy degree of skepticism. It is worth noting that these effects will rarely (if ever) occur all at once, although higher doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
There are currently 0 experience reports which describe the effects of this substance in our experience index.
Toxicity and harm potential
This toxicity and harm potential section is a stub.
As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
Oxymorphazone has a low toxicity relative to dose. It is estimated to be half to 100% as potent as oxymorphpne, suggesting that 10mg oxymorphazone is equivalent to approximately 30mg morphine. As with all opioids, long-term effects can vary but can include diminished libido, apathy, and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.
Oxymorphazone use is considered extremely dangerous. This is because if overdose occurs, antagonism of the μ-opioid receptor is not possible. Drugs such as naloxone are unable to knock oxymorphazone off the MOR, and as such are useless in treating oxymorphazone overdose. There are no MOR hydrazone antagonists (that would knock oxymorphazone off the MOR) on the market. Treatment of oxymorphazone overdose would be supportive care (such as mechanical ventilation) and ensuring the patient does not aspirate on their vomit.
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As with other opioids, the chronic use of oxymorphazone can be considered extremely addictive with a high potential for abuse and is capable of causing psychological and physical dependence among certain users. A single administration of oxymorphazone results in physical dependence in rats . Tolerance also builds extremely rapidly, due to its prolonged effects. Thus, although oxymorphazone may have similar subjective effects to oxymorphone, it is likely addiction would develop in a much larger proportion of users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.
Tolerance to many of the effects of oxymorphazone develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Oxymorphazone presents cross-tolerance with all other opioids, meaning that after the consumption of oxymorphazone all opioids will have a reduced effect. The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance. To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment one is in can play a role in opioid tolerance. In one scientific study, rats with the same history of oxymorphazone administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment.
Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when taken with other substances. The following lists some known dangerous combinations, but cannot be guaranteed to include all of them. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.
- Depressants (1,4-Butanediol, 2M2B, alcohol, benzodiazepines, barbiturates, GHB/GBL, methaqualone, opioids) - This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration. There is also an increased risk of suffocating on one's vomit while unconscious. If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Stimulants - It can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.
- Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- United Kingdom - Oxymorphazone is a Class A, Schedule 2 drug in the United Kingdom. It has no medical uses. 
- United States - Oxymorphazone is a Schedule I Controlled Substance in the United States. It is considered to be unsafe and holds no medical value. 
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- Receptor binding and analgesic properties of oxymorphazone. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6183551
- Irreversible opiate agonists and antagonists: the 14-hydroxydihydromorphinone azines. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6176696
- Discriminative stimulus effects of reversible and irreversible opiate agonists: morphine, oxymorphazone and buprenorphine. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6206224
- Ling, Geoffrey S. F.; Galetta, Steven; Pasternak, Gavril W. (1984). "Oxymorphazone: A long-acting opiate analgesic". Cellular and Molecular Neurobiology. 4 (1): 1–13. doi:10.1007/BF00710938. ISSN 0272-4340.
- Pergolizzi, Joseph V.; Raffa, Robert B. (2009). "Oxymorphone and Opioid Rotation". Pain Medicine. 10 (suppl 1): S39–S48. doi:10.1111/j.1526-4637.2009.00598.x. ISSN 1526-2375.
- Friedman, L. F. (2014, February 03). Why heroin relapse often ends in death. Retrieved from http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
- Siegel, S; Hinson, R.; Krank, M.; McCully, J (1982). "Heroin "overdose" death: contribution of drug-associated environmental cues". Science. 216 (4544): 436–437. doi:10.1126/science.7200260. ISSN 0036-8075.
- Psychoactive Substances Act 2016. (2016). Retrieved from http://www.legislation.gov.uk/ukpga/2016/2/schedule/2/enacted
- Drug Enforcement Administration Controlled Substances | https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf