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| Trade names | Dalgan |
| Other names | WY-16,225; WY-16225 |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Routes of administration | Intravenous infusion,intramuscular injection[1] |
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| Metabolism | Hepatic |
| Eliminationhalf-life | 2.2 hours |
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| Formula | C16H23NO |
| Molar mass | 245.366 g·mol−1 |
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Dezocine, sold under the brand nameDalgan, is an atypicalopioidanalgesic which is used in the treatment ofpain.[1][2] It is used byintravenous infusion andintramuscular injection.[1][2]
Dezocine is anopioid receptormodulator, acting as apartial agonist of theμ- andκ-opioid receptors.[2] It is abiased agonist of the μ-opioid receptor.[3][4] The drug has a similar profile of effects to related opioids acting at the μ-opioid receptor, includinganalgesia andeuphoria.[2][5] Unlike other opioids acting at the κ-opioid receptor however, dezocine does not produceside effects such asdysphoria orhallucinations at any therapeutically used dose.[6]
Dezocine was first synthesized in 1970.[7] It was introduced for medical use in theUnited States in 1986 but was not marketed in other countries.[2][8] 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 inChina.[2] In light of theopioid epidemic, dezocine has seen a resurgence in use and interest.[2]
Dezocine is generally administeredintravenously (as Dalgan) to relievepost-operativepain in patients.[1] It can also be administered inintramuscular doses, and is given once rather than continuously. It is often administered in post-operativelaparoscopy patients as an alternative tofentanyl. Dezocine haspotentanalgesic effects, and comparable or greater pain-relieving ability thanmorphine,codeine, andpethidine (meperidine).[9][10] It is a more effective analgesic thanpentazocine, but causes relatively morerespiratory depression.[11] Dezocine is a useful drug for the treatment of pain,[1] butside effects such asdizziness limit its clinical application,[12] and it can produceopioid withdrawal syndrome in patients alreadydependent on other opioids.[13] Because of its high efficacy, dezocine is often administered at a base dose of 0.1 mg/kg.Respiratory depression, aside effect of dezocine, reaches a ceiling at 0.3 to 0.4 mg/kg.
Side effects at lower doses include mild gastrointestinal discomfort and dizziness. Because decozine has mixed agonist/antagonist effects at theopioid receptors, it has a lowereddependence 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 anaddiction. Its efficacy as an analgesic is dose-dependent; however, it displays aceiling effect in induced respiratory depression at 0.3 to 0.4 mg/kg.
| Opioid | Opioid receptoraffinity (Ki, nM) | |||
|---|---|---|---|---|
| MORTooltip μ-Opioid receptor | KORTooltip κ-Opioid receptor | DORTooltip 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 anopioid receptorreceptor modulator.[2] It is specifically amixed agonist–antagonist orpartial agonist of theμ- andκ-opioid receptors.[2][15][16][17] It is abiased agonist of the μ-opioid receptor and activatesG protein signaling but not theβ-arrestin pathway.[3][4] This may account for some of dezocine's unique and atypical pharmacological properties.[3][4] Thebinding affinity of dezocine varies depending on the opioid receptor, with the drug having the highest affinity for the μ-opioid receptor, intermediate affinity for the κ-opioid receptor, and the lowest affinity for theδ-opioid receptor.[2] In addition to its opioid activity, dezocine has been found to act as aserotonin–norepinephrine reuptake inhibitor (SNRI), withpIC50 values of 5.86 for theserotonin transporter (SERT) and 5.68 for thenorepinephrine transporter (NET).[14][18] These actions theoretically might contribute to its analgesic efficacy.[2]
Dezocine is five times as potent aspethidine and one-fifth as potent asbutorphanol as an analgesic.[1] Due to its partial agonist nature at the μ-opioid receptor, dezocine has significantly reduced side effects relative to opioid analgesics acting asfull agonists of the receptor such asmorphine.[14] Moreover, dezocine is not acontrolled substance and there are no reports ofaddiction related to its use, indicating that, unlike virtually all other clinically employed μ-opioid receptor agonists (including weak partial agonists likebuprenorphine), and for reasons that are not fully clear, it is apparently non-addictive.[14] 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.[19]
Dezocine has abioavailability byintramuscular injection of 97%.[20] It has a mean t1/2α of fewer than two minutes, and itsbiological half-life is 2.2 hours.[citation needed]
Dezocine has a structure similar to thebenzomorphan group of opioids. Dezocine is unusual among opioids as it is one of the onlyprimary amines known to beactive as an opioid (along withbisnortilidine, anactive metabolite oftilidine).[2][additional citation(s) needed]
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.[21]
The synthesis of dezocine begins with thecondensation of 1-methyl-7-methoxy-2-tetralone with 1,5-dibromopentane through use ofNaH orpotassium tert-butoxide.[22] This yields 1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone, which is then cyclized with NaH to produce 5-methyl-3-methoxy-5,6,7,8,9,10,11,12-octahydro-5,11-methanobenzocyclodecen-13-one. The product is then treated withhydroxylamine hydrochloride, to yield anoxime. Areduction reaction inhydrogen gas produces anisomeric mixture, from which the final product is crystallized and cleaved withHBr.
Dezocine was patented byAmerican 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,[23] dezocine's usage is discontinued in the United States, but it is still widely used in some other countries such asChina.[2][24]
Dezocine is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andUSANTooltip United States Adopted Name.[25][26][27][8]
The major brand name of dezocine is Dalgan.[8]
In 2000, dezocine was listed as being marketed only in theUnited States.[8] It has since been marketed inChina.[2] Dezocine was discontinued in the United States in 2011.[2]
As of 2011, dezocine is not used in theUnited States orCanada. It is not commercially available in either of these countries,[23] nor is it offered as a prescribed analgesic for postoperative care. InChina however, it is commonly used after surgery.[9]
Dezocine showsantidepressant-like effects in animals.[3][28][29] Its antidepressant-like effects in animals appear to be dependent on activation ofserotonin5-HT1A receptors and inhibition ofκ-opioid receptors (KORs) but not on activation of theμ-opioid receptor.[3][28][29] Aclinical trial found that dezocine added tosufentanil forpostoperativeanalgesia significantly reduceddepressive symptoms in people undergoingcolorectal cancersurgery relative to sufentanil alone.[3][28][30] There is acase report of a single incidental dose of dezocine resulting in rapid and sustained improvement in depression,anhedonia, andmotivational deficits in a woman withtreatment-resistant depression.[31] On the basis of the preceding findings, there is interest in dezocine as a potential antidepressant in the treatment of depression, for instance in people withopioid use disorder.[3][4]
6.3 Antidepressant actions: In a study of postoperative depression, which is common among patients undergoing cancer surgery, patients who received dezocine in addition to a pain medication had lower scores on the Beck Depression Inventory than did patients who received the pain medication alone.32 In mouse models of "depressive-like" behaviors—the forced swim task and tail suspension task—immobility is used as a proxy for the clinical state. In both tasks, dezocine dose-dependently reduced immobility, with no other motor effects. The reduction in immobility was blocked by the serotonin 1A receptor antagonist Way100635 and by the κopioid receptor agonist U50,488, consistent with dezocine acting via serotonin and κ-opioid receptors.31 [...] Given that depression often co-occurs with OUD,55,56 these pharmacological effects of dezocine could be beneficial in treating OUD [...] Dezocine may have antidepressant activity that could be helpful in treating persons with OUD.
Dezocine has been found to inhibit both the serotonin and norepinephrine uptake transporters [1]. This led to the investigation and discovery that dezocine has antidepressant activity in patients treated post-operatively for pain [22]. Anti-depressant activity of dezocine was also verified in a rodent model [23]. It has been known that depression is a major comorbidity in chronic pain and opioid use disorder [24]. Substituting dezocine for methadone or buprenorphine for opioid use disorder would have the added benefit of treating the major comorbidity depression along with its other favorable properties of reduced respiratory depression and lack of addiction.
Treatment with dezocine combined with sufentanil can significantly reduce the symptoms of postoperative depression and improve sleep quality in patients (Zhao et al. 2020), because of the antidepressant efects of dezocine that appear to be mediated by 5-HT1A receptors and κ-opioid receptors (Shang et al. 2021).
