Cyprenorphine (M285), N-cyclo-propylmethyl-6,14-endoetheno-7α-(1-hydroxy-1-methylethyl)-6,7,8,14-tetrahydronororipavine, is an

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

drug. It is related to more well-known opioids such as

buprenorphine Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...

, which is used as an analgesic and for the treatment of

opioid addiction Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Op ...

, and

diprenorphine Diprenorphine (brand name Revivon; former developmental code name M5050), also known as diprenorfin, is a non-selective, high- affinity, weak partial agonist of the μ- (MOR), κ- (KOR), and δ-opioid receptor (DOR) (with equal affinity) which ...

, which is used as an

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

to reverse the effects of other opioids. It is roughly 35 times as strong as nalorphine. Cyprenorphine is a powerful antagonist of opioid receptors and a highly potent specific antagonist. It blocks the binding of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

and

etorphine Etorphine (M99) is a semi-synthetic opioid possessing an analgesic potency approximately 1,000–3,000 times that of morphine. It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather the r ...

to these receptors. Cyprenorphine has mixed agonist–antagonist effects at opioid receptors, like those of buprenorphine. However the effects of cyprenorphine are somewhat different, as it produces pronounced dysphoric and

hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...

effects which limit its potential use as an analgesic. Cyprenorphine also has been shown to suppress the intake of sweet solution but doesn't suppress the increase in food consumption that is produced by the alpha-2-adrenoceptor antagonist

idazoxan Idazoxan ( INN) is a drug which is used in scientific research. It acts as both a selective α2 adrenergic receptor antagonist, and an antagonist for the imidazoline receptor. Idazoxan has been under investigation as an antidepressant, but it d ...

. Idazoxan may lead to the release of endogenous opioid peptides and increase food intake, this effect is attenuated by (-)-naloxone but not by the mu/delta-antagonist cyprenorphine.

Medical uses

Cyprenorphine increases locomotor activity. It is normally used to reverse the clinically immobilizing effects of etorphine. These effects are reversed rapidly and almost entirely. Etorphine is a chemical relative of morphine, with similar analgesic characteristics but fewer side effects. For instance, in order to handle polar bears and other large animals, they are immobilized using etorphine and the effects of etorphine reversed as soon as handling is complete using cyprenorphine. Etorphine and cyprenorphine come as white powders in a package and cannot be purchased separately. Both are administered by injection after dissolving in saline. Because etorphine is used to immobilize large, still moving, animals, it is often administered intramuscularly using a dart whereas cyprenorphine can be administered

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

in the femoral vein of the immobile animal. Unlike other antagonists, used to reverse the effects of etorphine, the dose of cyprenorphine administered depends on the initial dose of etorphine instead of the weight of the animal. The recommended dose of cyprenorphine is three times that of the initial etrophine administered. Although the effects of cyprenorphine typically take from 40 to 60 seconds to kick in, it has been observed to take up to 3 hours in white rhinoceroses.

Adverse effects

Cyprenorphine induces depression over an hour in rats. It has also been found to induce

psychotomimetic A drug with psychotomimetic (also known as psychotogenic) actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administrati ...

actions in humans and dysphoria when used as a post-operative analgesic in patients. Because of these side effects, it is seldom used in humans, with

preferred instead.

Mechanism of action

Although it is still unclear how cyprenorphine antagonizes the effects of etorphine, it has been suggested that its greater

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

may enable it to displace etorphine in mutual binding sites in the brain. 16-methyl Cyprenorphine, an

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...

of Cyprenorphine is an antagonist of the delta, mu and kappa opioid receptors. Its

elimination rate constant The elimination rate constant ''K'' or ''Ke'' is a value used in pharmacokinetics to describe the rate at which a drug is removed from the human system. It is often abbreviated ''K'' or ''K'e''. It is equivalent to the fraction of a substance ...

s (Ke) at these receptors are 0.68, 0.076 and 0.79 nM respectively.

References

{{Opioidergics Tertiary alcohols Cycloalkenes 4,5-Epoxymorphinans Ethers Kappa-opioid receptor agonists Phenols Semisynthetic opioids