Dezocine

Source: Wikipedia, the free encyclopedia.
Dezocine
Intravenous infusion, intramuscular injection[1]
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Hepatic
Elimination half-life2.2 hours
Identifiers
  • (5R,11S,13R)-13-Amino-5-methyl-5,6,7,8,9,10,11,12-octahydro-5,11-methanobenzo[10]annulen-3-ol
JSmol)
  • Oc1ccc2c(c1)[C@@]3(C)CCCCC[C@@H](C2)[C@H]3N
  • InChI=1S/C16H23NO/c1-16-8-4-2-3-5-12(15(16)17)9-11-6-7-13(18)10-14(11)16/h6-7,10,12,15,18H,2-5,8-9,17H2,1H3/t12-,15-,16+/m0/s1 checkY
  • Key:VTMVHDZWSFQSQP-VBNZEHGJSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Dezocine, sold under the brand name Dalgan, is an atypical

intravenous infusion and intramuscular injection.[1][2]

Dezocine is an

analgesia and euphoria.[2][3] Unlike other opioids acting at the κ-opioid receptor however, dezocine does not produce side effects such as dysphoria or hallucinations at any therapeutically used dose.[4]

Dezocine was first synthesized in 1970.[5] It was introduced for medical use in the United States in 1986 but was not marketed in other countries.[2][6] Dezocine was discontinued in the United States in 2011 with no official reason given.[2] However, it has become one of the most widely used analgesics in China.[2] In light of the opioid epidemic, dezocine has seen a resurgence in use and interest.[2]

Medical uses

Dezocine is generally administered

Respiratory depression, a side effect
of dezocine, reaches a ceiling at 0.3 to 0.4 mg/kg.

Side effects

dependence potential than purely agonistic opioids. It can be prescribed, therefore, in small doses over an extended period of time without causing patients to develop and sustain an addiction. Its efficacy as an analgesic is dose-dependent; however, it displays a ceiling effect
in induced respiratory depression at 0.3 to 0.4 mg/kg.

Pharmacology

Pharmacodynamics

Opioid activity of dezocine and morphine[2][12]
Opioid
affinity
(Ki, nM)
MOR
Tooltip μ-Opioid receptor
KOR
Tooltip κ-Opioid receptor
DOR
Tooltip δ-Opioid receptor
Dezocine 3.67 ± 0.7 31.9 ± 1.9 527 ± 70
Morphine 2.8 ± 0.2 55.96 ± 6.99 648.8 ± 59.7

Dezocine acts as an

binding affinity of dezocine varies depending on the opioid receptor, with it having the highest affinity for the μ-opioid receptor, intermediate affinity for the κ-opioid receptor, and the lowest affinity for the δ-opioid receptor.[2] In addition to its opioid activity, dezocine has been found to act as a serotonin–norepinephrine reuptake inhibitor (SNRI), with pIC50 values of 5.86 for the serotonin transporter (SERT) and 5.68 for the norepinephrine transporter (NET).[12][16] These actions theoretically might contribute to its analgesic efficacy.[2]

Dezocine is five times as potent as

addiction related to its use, indicating that, unlike virtually all other clinically employed μ-opioid receptor agonists (including weak partial agonists like buprenorphine), and for reasons that are not fully clear, it is apparently non-addictive.[12] This unique benefit makes long-term low-dose treatment of chronic pain and/or opioid dependence with dezocine more feasible than with most other opioids. Despite having a stronger respiratory depressant effect than morphine, dezocine shows a ceiling effect on its respiratory depressive action so above a certain dose this effect does not get any more severe.[17]

Pharmacokinetics

Dezocine has an bioavailability by intramuscular injection of 97%.[18] It has a mean t1/2α of fewer than two minutes, and its biological half-life is 2.2 hours.[citation needed]

Chemistry

Dezocine has a structure similar to the

primary amines known to be active as an opioid (along with bisnortilidine, an active metabolite of tilidine).[2][additional citation(s) needed
]

Synthesis

Dezocine [(−)-13β-amino-5,6,7,8,9,10,11,12-octahydro-5α-methyl-5,11-methanobenzocyclodecen-31-ol, hydrobromide] is a pale white crystal powder. It has no apparent odor. The salt is soluble at 20 mg/ml, and a 2% solution has a pH of 4.6.[19]

The synthesis of dezocine begins with the

hydrogen gas produces an isomeric mixture, from which the final product is crystallized and cleaved with HBr
.

History

Dezocine was patented by

American Home Products Corp. in 1978. Clinical trials ran from 1979 to 1985, before its approval by the U.S. Food and Drug Administration (FDA) in 1986. As of 2011,[21] dezocine's usage is discontinued in the United States, but it is still widely used in some other countries such as China.[2][22]

Society and culture

Generic names

Dezocine is the

INNTooltip International Nonproprietary Name and USANTooltip United States Adopted Name.[23][24][25][6]

Brand names

The major brand name of dezocine is Dalgan.[6]

Availability

In 2000, dezocine was listed as being marketed only in the United States.[6] It has since been marketed in China.[2] Dezocine was discontinued in the United States in 2011.[2]

Legal status

As of 2011, dezocine is not used in the United States or Canada. It is not commercially available in either of these countries,[21] nor is it offered as a prescribed analgesic for postoperative care. In China however, it is commonly used after surgery.[7]

References

  1. ^
    S2CID 195697572
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  2. ^
    PMID 34141081
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  3. S2CID 34394471
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  4. doi:10.1097/00001503-199108000-00017
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  5. ^ "Espacenet". Espacenet Patent Search.
  6. ^
    ISBN 9783887630751
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  7. ^
    PMID 12513698
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  8. PMID 398127
    .
  9. S2CID 45928473
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  10. PMID 7363647
    .
  11. S2CID 10183991
    .
  12. ^
    PMID 24263237
    .
  13. PMID 30237513
    .
  14. PMID 16433932
    .
  15. PMID 6142942
    .
  16. PMID 28230181
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  17. S2CID 19569628
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  18. S2CID 20426334
    .
  19. PMID 808600
    .
  20. PMID 4714986
    .
  21. ^ a b "FDA Drugs". Archived from the original on 2013-01-27. Retrieved 2012-11-01.
  22. PMID 28533424
    .
  23. ISBN 978-1-4757-2085-3
    .
  24. ISBN 9789401144391
    .
  25. ISBN 9788122415650
    .
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