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 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 etorphine 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. and dysphoria when used as a post-operative analgesic in patients. Because of these side effects, it is seldom used in humans, with diprenorphine 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 may enable it to displace etorphine in mutual binding sites in the brain. 16-methyl Cyprenorphine, an isoform of Cyprenorphine is an antagonist of the delta, mu and kappa opioid receptors. Its elimination rate constants (Ke) at these receptors are 0.68, 0.076 and 0.79 nM respectively.

References

References

1. (April 1968). "Effect of cyprenorphine (M285), a morphine antagonist, on the distribution and excretion of etorphine (M99), a potent morphine-like drug". The Journal of Pharmacology and Experimental Therapeutics.
2. (January 1990). "Centrally administered opioid antagonists, nor-binaltorphimine, 16-methyl cyprenorphine and MR2266, suppress intake of a sweet solution". Pharmacology, Biochemistry, and Behavior.
3. (1971). "Etorphine hydrochloride antagonists used in the capture of the white rhinoceros Ceratotherium simum simum.". Lammergeyer.
4. (April 1965). "Compounds possessing Morphine-antagonizing or Powerful Analgesic Properties". Nature.
5. (December 1969). "Some effects of a hallucinogenic compound (cyprenorphine hydrochloride; M 285) on the light reinforced behaviour of rats". Nature.
6. (August 1992). "Endogenous opioids may be involved in idazoxan-induced food intake". Neuropharmacology.
7. (1971). "The behavioural effects of levallorphan, cyprenorphine (M285) and amphetamine on repeated Y-maze performance in rats". Psychopharmacologia.
8. (1976). "Use of M99 Etorphine and Antagonists to Immobilize and Handle Black Bears". Bears: Their Biology and Management.
9. (1972). "The effect of LSD-25 on light-reinforced behaviour in the rat". Psychopharmacologia.
10. "In Pursuit of the Holy Grail". Nathan B. Eddy Award lecture.
11. (November 1974). "Proceedings: Brain levels of the potent analgesic etorphine in rats and their functional significance". British Journal of Pharmacology.
12. (January 1987). "16-Me cyprenorphine (RX 8008M): a potent opioid antagonist with some delta selectivity". Life Sciences.