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]
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.
Dezocine is five times as potent as pethidine and one-fifth as potent as butorphanol 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 as full agonists of the receptor such as morphine.[12] 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.[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]
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 condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-dibromopentane through use of NaHorpotassium tert-butoxide.[20] 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 reactioninhydrogen gas produces an isomeric mixture, from which the final product is crystallized and cleaved with HBr.
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]
Dezocine is the generic name of the drug and its INNTooltip International Nonproprietary Name and USANTooltip United States Adopted Name.[23][24][25][6]
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]
As of 2011, dezocine is not used in the United StatesorCanada. 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]
^Oosterlinck W, Verbaeys A (1980). "Preliminary clinical experience with dezocine, a new potent analgesic". Current Medical Research and Opinion. 6 (7): 472–4. doi:10.1185/03007998009109470. PMID7363647.
^Strain EC, Preston KL, Liebson IA, Bigelow GE (August 1996). "Opioid antagonist effects of dezocine in opioid-dependent humans". Clinical Pharmacology and Therapeutics. 60 (2): 206–17. doi:10.1016/S0009-9236(96)90137-X. PMID8823239. S2CID10183991.
^Romagnoli A, Keats AS (March 1984). "Ceiling respiratory depression by dezocine". Clinical Pharmacology and Therapeutics. 35 (3): 367–73. doi:10.1038/clpt.1984.45. PMID6421529. S2CID19569628.
^Locniskar A, Greenblatt DJ, Zinny MA (1986). "Pharmacokinetics of dezocine, a new analgesic: effect of dose and route of administration". European Journal of Clinical Pharmacology. 30 (1): 121–3. doi:10.1007/bf00614208. PMID3709625. S2CID20426334.
^Malis JL, Rosenthale ME, Gluckman MI (September 1975). "Animal pharmacology of Wy-16,225, a new analgesic agent". The Journal of Pharmacology and Experimental Therapeutics. 194 (3): 488–98. PMID808600.