Dezocine

{{Short description|Opioid analgesic}} {{cs1 config|name-list-style=vanc}} {{Infobox drug | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 460779162 | IUPAC_name = (5''R'',11''S'',13''R'')-13-Amino-5-methyl-5,6,7,8,9,10,11,12-octahydro-5,11-methanobenzo[10]annulen-3-ol | image = Dezocine.svg | image_class = skin-invert-image | width = 200px | image2 = Dezocine molecule ball.png | image_class2 = bg-transparent | width2 = 200px

| tradename = Dalgan | Drugs.com = {{drugs.com|CONS|dezocine}} | pregnancy_category = | legal_status = Rx-only | routes_of_administration = Intravenous infusion, intramuscular injection<ref name="pmid2670517" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 53648-55-8 | ATC_prefix = N02 | ATC_suffix = AX03 | PubChem = 3033053 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01209 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2297867 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = VHX8K5SV4X | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00838 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 4474 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1685 | synonyms = WY-16,225; WY-16225

| C=16 | H=23 | N=1 | O=1 | SMILES = Oc1ccc2c(c1)[C@@]3(C)CCCCC[C@@H](C2)[C@H]3N | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VTMVHDZWSFQSQP-VBNZEHGJSA-N }}

'''Dezocine''', sold under the brand name '''Dalgan''', is an atypical opioid analgesic which is used in the treatment of pain.<ref name="pmid2670517">{{cite journal | vauthors = O'Brien JJ, Benfield P | title = Dezocine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy | journal = Drugs | volume = 38 | issue = 2 | pages = 226–48 | date = August 1989 | pmid = 2670517 | doi = 10.2165/00003495-198938020-00005 | s2cid = 195697572 | url = }}</ref><ref name="pmid34141081">{{cite journal | vauthors = Childers WE, Abou-Gharbia MA | title = "I'll Be Back": The Resurrection of Dezocine | journal = ACS Med Chem Lett | volume = 12 | issue = 6 | pages = 961–968 | date = June 2021 | pmid = 34141081 | doi = 10.1021/acsmedchemlett.1c00233 | pmc = 8201756 | url = }}</ref> It is used by intravenous infusion and intramuscular injection.<ref name="pmid2670517" /><ref name="pmid34141081" />

Dezocine is an opioid receptor modulator, acting as a partial agonist of the μ- and κ-opioid receptors.<ref name="pmid34141081" /> It is a biased agonist of the μ-opioid receptor.<ref name="BarrSchmidtThakrar2024" /><ref name="GrothusenLinXi2022" /> The drug has a similar profile of effects to related opioids acting at the μ-opioid receptor, including analgesia and euphoria.<ref name="pmid34141081" /><ref name="pmid1348168">{{cite journal | vauthors = Zacny JP, Lichtor JL, de Wit H | title = Subjective, behavioral, and physiologic responses to intravenous dezocine in healthy volunteers | journal = Anesthesia and Analgesia | volume = 74 | issue = 4 | pages = 523–30 | date = April 1992 | pmid = 1348168 | doi = 10.1213/00000539-199204000-00010 | s2cid = 34394471 | doi-access = free }}</ref> 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.<ref name="Westmoreland1991">{{cite journal | vauthors = Westmoreland C | date = August 1991 | title = Opioid agonist-antagonists | journal = Current Opinion in Anesthesiology | volume = 4 | issue = 4 | pages = 556–562 | doi = 10.1097/00001503-199108000-00017 }}</ref>

Dezocine was first synthesized in 1970.<ref>{{cite web|title=Espacenet|url=http://worldwide.espacenet.com/publicationDetails/biblio?CC=DE&NR=2159324&KC=&FT=E&locale=en_EP|location=Espacenet Patent Search}}</ref> It was introduced for medical use in the United States in 1986 but was not marketed in other countries.<ref name="pmid34141081" /><ref name="SwissPharmaceuticalSociety2000" /> Dezocine was discontinued in the United States in 2011 with no official reason given.<ref name="pmid34141081" /> However, it has become one of the most widely used analgesics in China.<ref name="pmid34141081" /> In light of the opioid epidemic, dezocine has seen a resurgence in use and interest.<ref name="pmid34141081" />

==Medical uses== Dezocine is generally administered intravenously (as Dalgan) to relieve post-operative pain in patients.<ref name="pmid2670517" /> It can also be administered in intramuscular doses, and is given once rather than continuously. It is often administered in post-operative laparoscopy patients as an alternative to fentanyl. Dezocine has potent analgesic effects, and comparable or greater pain-relieving ability than morphine, codeine, and pethidine (meperidine).<ref name="Gharagozlou" /><ref>{{cite journal | vauthors = Camu F, Gepts E | title = Analgesic properties of dezocine for relief of postoperative pain | journal = Acta Anaesthesiologica Belgica | volume = 30 | issue = Suppl | pages = 183–91 | year = 1979 | pmid = 398127 }}</ref> It is a more effective analgesic than pentazocine, but causes relatively more respiratory depression.<ref>{{cite journal | vauthors = Wuest HP, Bellville JW | title = The respiratory effects of dezocine and pentazocine in man | journal = Journal of Clinical Pharmacology | volume = 19 | issue = 4 | pages = 205–10 | date = April 1979 | pmid = 438355 | doi = 10.1002/j.1552-4604.1979.tb01653.x | s2cid = 45928473 }}</ref> Dezocine is a useful drug for the treatment of pain,<ref name="pmid2670517" /> but side effects such as dizziness limit its clinical application,<ref>{{cite journal | vauthors = Oosterlinck W, Verbaeys A | title = Preliminary clinical experience with dezocine, a new potent analgesic | journal = Current Medical Research and Opinion | volume = 6 | issue = 7 | pages = 472–4 | year = 1980 | pmid = 7363647 | doi = 10.1185/03007998009109470 }}</ref> and it can produce opioid withdrawal syndrome in patients already dependent on other opioids.<ref>{{cite journal | vauthors = Strain EC, Preston KL, Liebson IA, Bigelow GE | title = Opioid antagonist effects of dezocine in opioid-dependent humans | journal = Clinical Pharmacology and Therapeutics | volume = 60 | issue = 2 | pages = 206–17 | date = August 1996 | pmid = 8823239 | doi = 10.1016/S0009-9236(96)90137-X | s2cid = 10183991 }}</ref> Because of its high efficacy, dezocine is often administered at a base dose of 0.1 mg/kg. Respiratory depression, a side effect of dezocine, reaches a ceiling at 0.3 to 0.4 mg/kg.

==Side effects== Side effects at lower doses include mild gastrointestinal discomfort and dizziness. Because decozine has mixed agonist/antagonist effects at the opioid receptors, it has a lowered 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=== {| class="wikitable floatright" |+ Opioid activity of dezocine and morphine<ref name="pmid34141081" /><ref name="LiuHuang2014">{{cite journal | vauthors = Liu R, Huang XP, Yeliseev A, Xi J, Roth BL|author5-link=Bryan Roth | title = Novel molecular targets of dezocine and their clinical implications | journal = Anesthesiology | volume = 120 | issue = 3 | pages = 714–23 | date = March 2014 | pmid = 24263237 | pmc = 3944410 | doi = 10.1097/ALN.0000000000000076 }}</ref> |- ! rowspan="2" | Opioid ! colspan="4" | Opioid receptor affinity (Ki, nM) |- ! {{Abbrlink|MOR|μ-Opioid receptor}} ! {{Abbrlink|KOR|κ-Opioid receptor}} ! {{Abbrlink|DOR|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 opioid receptor receptor modulator.<ref name="pmid34141081" /> It is specifically a mixed agonist–antagonist or partial agonist of the μ- and κ-opioid receptors.<ref name="pmid34141081" /><ref name="pmid30237513">{{cite journal | vauthors = Wang YH, Chai JR, Xu XJ, Ye RF, Zan GY, Liu GY, Long JD, Ma Y, Huang X, Xiao ZC, Dong H, Wang YJ | title = Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a κ Partial Agonist and μ Partial Agonist | journal = Sci Rep | volume = 8 | issue = 1 | page = 14087 | date = September 2018 | pmid = 30237513 | pmc = 6148296 | doi = 10.1038/s41598-018-32568-y | bibcode = 2018NatSR...814087W | url = }}</ref><ref>{{cite journal | vauthors = Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J | title = Pharmacological profiles of opioid ligands at kappa opioid receptors | journal = BMC Pharmacology | volume = 6 | page = 3 | date = January 2006 | pmid = 16433932 | pmc = 1403760 | doi = 10.1186/1471-2210-6-3 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Young AM, Stephens KR, Hein DW, Woods JH | title = Reinforcing and discriminative stimulus properties of mixed agonist-antagonist opioids | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 229 | issue = 1 | pages = 118–26 | date = April 1984 | pmid = 6142942 }}</ref> It is a biased agonist of the μ-opioid receptor and activates G protein signaling but not the β-arrestin pathway.<ref name="BarrSchmidtThakrar2024" /><ref name="GrothusenLinXi2022" /> This may account for some of dezocine's unique and atypical pharmacological properties.<ref name="BarrSchmidtThakrar2024" /><ref name="GrothusenLinXi2022" /> The binding 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 the δ-opioid receptor.<ref name="pmid34141081" /> 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).<ref name="LiuHuang2014" /><ref name="pmid28230181">{{cite journal | vauthors = Wang YX, Mao XF, Li TF, Gong N, Zhang MZ | title = Dezocine exhibits antihypersensitivity activities in neuropathy through spinal μ-opioid receptor activation and norepinephrine reuptake inhibition | journal = Scientific Reports | volume = 7 | issue = | article-number = 43137 | date = February 2017 | pmid = 28230181 | pmc = 5322378 | doi = 10.1038/srep43137 | bibcode = 2017NatSR...743137W }}</ref> These actions theoretically might contribute to its analgesic efficacy.<ref name="pmid34141081" />

Dezocine is five times as potent as pethidine and one-fifth as potent as butorphanol as an analgesic.<ref name="pmid2670517" /> Due to its partial agonist nature at the μ-opioid receptor, dezocine has significantly reduced side effects relative to opioid analgesics acting as full agonists of the receptor such as morphine.<ref name="LiuHuang2014" /> Moreover, dezocine is not a controlled substance and there are no reports of 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.<ref name="LiuHuang2014" /> 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.<ref>{{cite journal | vauthors = Romagnoli A, Keats AS | title = Ceiling respiratory depression by dezocine | journal = Clinical Pharmacology and Therapeutics | volume = 35 | issue = 3 | pages = 367–73 | date = March 1984 | pmid = 6421529 | doi = 10.1038/clpt.1984.45 | s2cid = 19569628 }}</ref>

===Pharmacokinetics=== Dezocine has a bioavailability by intramuscular injection of 97%.<ref name="pmid3709625">{{cite journal | vauthors = Locniskar A, Greenblatt DJ, Zinny MA | title = Pharmacokinetics of dezocine, a new analgesic: effect of dose and route of administration | journal = European Journal of Clinical Pharmacology | volume = 30 | issue = 1 | pages = 121–3 | year = 1986 | pmid = 3709625 | doi = 10.1007/bf00614208 | s2cid = 20426334 }}</ref> It has a mean t1/2α of fewer than two minutes, and its biological half-life is 2.2 hours.{{Citation needed|date=October 2021}}

==Chemistry== Dezocine has a structure similar to the benzomorphan group of opioids. Dezocine is unusual among opioids as it is one of the only primary amines known to be active as an opioid (along with bisnortilidine, an active metabolite of tilidine).<ref name="pmid34141081" />{{Additional citation needed|date=October 2021}}

===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.<ref>{{cite journal | vauthors = Malis JL, Rosenthale ME, Gluckman MI | title = Animal pharmacology of Wy-16,225, a new analgesic agent | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 194 | issue = 3 | pages = 488–98 | date = September 1975 | pmid = 808600 }}</ref>

The synthesis of dezocine begins with the condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-dibromopentane through use of NaH or potassium tert-butoxide.<ref>{{cite journal | vauthors = Freed ME, Potoski JR, Freed EH, Conklin GL, Malis JL | title = Bridged aminotetralins as novel potent analgesic sunstances | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 6 | pages = 595–9 | date = June 1973 | pmid = 4714986 | doi = 10.1021/jm00264a003 }}</ref> 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 with hydroxylamine hydrochloride, to yield an oxime. A reduction reaction in 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,<ref name="FDA Drugs">{{cite web|title=FDA Drugs|url=http://fdadrugs.legalview.com/legal-issue/dalgan|access-date=2012-11-01|archive-url=https://archive.today/20130127212955/http://fdadrugs.legalview.com/legal-issue/dalgan|archive-date=2013-01-27}}</ref> dezocine's usage is discontinued in the United States, but it is still widely used in some other countries such as China.<ref name="pmid34141081" /><ref name="pmid28533424">{{cite journal | vauthors = Wang L, Liu X, Wang J, Sun Y, Zhang G, Liang L | title = Comparison of the efficacy and safety between dezocine injection and morphine injection for persistence of pain in Chinese cancer patients: a meta-analysis | journal = Bioscience Reports | volume = 37 | issue = 3 | pages = | date = June 2017 | pmid = 28533424 | pmc = 5463259 | doi = 10.1042/BSR20170243 }}</ref>

==Society and culture==

===Generic names=== ''Dezocine'' is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|USAN|United States Adopted Name}}.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA368|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=368–}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | year = 2012 | title = Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher = Springer Science & Business Media | page = 96 | isbn = 978-94-011-4439-1 | url = https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA96}}</ref><ref name="Kar2005">{{cite book | vauthors = Kar A | year = 2005 | title = Medicinal Chemistry | publisher = New Age International | page = 268 | isbn = 978-81-224-1565-0 | url = https://books.google.com/books?id=07g30rxCA0EC&pg=PA268}}</ref><ref name="SwissPharmaceuticalSociety2000">{{cite book | editor = Swiss Pharmaceutical Society | author = Swiss Pharmaceutical Society | year = 2000 | title = Index Nominum 2000: International Drug Directory | publisher = Taylor & Francis | page = 320 | isbn = 978-3-88763-075-1 | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA320}}</ref>

===Brand names=== The major brand name of dezocine is Dalgan.<ref name="SwissPharmaceuticalSociety2000" />

===Availability=== In 2000, dezocine was listed as being marketed only in the United States.<ref name="SwissPharmaceuticalSociety2000" /> It has since been marketed in China.<ref name="pmid34141081" /> Dezocine was discontinued in the United States in 2011.<ref name="pmid34141081" />

===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,<ref name="FDA Drugs"/> nor is it offered as a prescribed analgesic for postoperative care. In China however, it is commonly used after surgery.<ref name="Gharagozlou">{{cite journal | vauthors = Gharagozlou P, Demirci H, David Clark J, Lameh J | title = Activity of opioid ligands in cells expressing cloned mu opioid receptors | journal = BMC Pharmacology | volume = 3 | page = 1 | date = January 2003 | pmid = 12513698 | pmc = 140036 | doi = 10.1186/1471-2210-3-1 | doi-access = free }}</ref>

==Research== ===Depression=== Dezocine shows antidepressant-like effects in animals.<ref name="BarrSchmidtThakrar2024">{{cite journal | vauthors = Barr GA, Schmidt HD, Thakrar AP, Kranzler HR, Liu R | title = Revisiting dezocine for opioid use disorder: A narrative review of its potential abuse liability | journal = CNS Neurosci Ther | volume = 30 | issue = 9 | article-number = e70034 | date = September 2024 | pmid = 39295098 | pmc = 11410865 | doi = 10.1111/cns.70034 | url = | quote = 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.}}</ref><ref name="Vázquez-LeónMiranda-PáezValencia-Flores2023">{{cite journal | vauthors = Vázquez-León P, Miranda-Páez A, Valencia-Flores K, Sánchez-Castillo H | title = Defensive and Emotional Behavior Modulation by Serotonin in the Periaqueductal Gray | journal = Cell Mol Neurobiol | volume = 43 | issue = 4 | pages = 1453–1468 | date = May 2023 | pmid = 35902460 | doi = 10.1007/s10571-022-01262-z | url = | quote = 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).| pmc = 11412428 }}</ref><ref name="ShangDuanChang2021">{{cite journal | vauthors = Shang L, Duan C, Chang S, Chang N, Jia S | title = Antidepressant-like effects of dezocine in mice: involvement of 5-HT1A and κ opioid receptors | journal = Behav Pharmacol | volume = 32 | issue = 6 | pages = 472–478 | date = September 2021 | pmid = 34101632 | doi = 10.1097/FBP.0000000000000641 | url = }}</ref> Its antidepressant-like effects in animals appear to be dependent on activation of serotonin 5-HT1A receptors and inhibition of κ-opioid receptors (KORs) but not on activation of the μ-opioid receptor.<ref name="BarrSchmidtThakrar2024" /><ref name="Vázquez-LeónMiranda-PáezValencia-Flores2023" /><ref name="ShangDuanChang2021" /> A clinical trial found that dezocine added to sufentanil for postoperative analgesia significantly reduced depressive symptoms in people undergoing colorectal cancer surgery relative to sufentanil alone.<ref name="BarrSchmidtThakrar2024" /><ref name="Vázquez-LeónMiranda-PáezValencia-Flores2023" /><ref name="ZhaoWuLi2020">{{cite journal | vauthors = Zhao P, Wu Z, Li C, Yang G, Ding J, Wang K, Wang M, Feng L, Duan G, Li H | title = Postoperative analgesia using dezocine alleviates depressive symptoms after colorectal cancer surgery: A randomized, controlled, double-blind trial | journal = PLOS ONE | volume = 15 | issue = 5 | article-number = e0233412 | date = 2020 | pmid = 32453759| pmc = 7250456 | doi = 10.1371/journal.pone.0233412 | doi-access = free | bibcode = 2020PLoSO..1533412Z | url = }}</ref> There is a case report of a single incidental dose of dezocine resulting in rapid and sustained improvement in depression, anhedonia, and motivational deficits in a woman with treatment-resistant depression.<ref name="WangLyuZhao2024">{{cite journal | vauthors = Wang H, Lyu N, Zhao Q | title = Case report: Dezocine's rapid and sustained antidepressant effects | journal = Front Pharmacol | volume = 15 | issue = | article-number = 1411119 | date = 2024 | pmid = 39092225 | pmc = 11291242 | doi = 10.3389/fphar.2024.1411119 | doi-access = free | url = }}</ref> 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 with opioid use disorder.<ref name="BarrSchmidtThakrar2024" /><ref name="GrothusenLinXi2022">{{cite journal | vauthors = Grothusen J, Lin W, Xi J, Zanni G, Barr GA, Liu R | title = Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor | journal = Transl Perioper Pain Med | volume = 9 | issue = 1 | pages = 424–429 | date = 2022 | pmid = 35572183 | pmc = 9097853 | doi = | url = | quote = 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.}}</ref>

==References== {{Reflist}}

Category:Biased ligands Category:Kappa-opioid receptor antagonists Category:Opioids Category:Serotonin–norepinephrine reuptake inhibitors Category:Phenols Category:Amines Category:Tricyclic compounds