Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Dezocine (INN, CAS 53648- 55-8), chemically (-)-13-amino-5,6,7,8,9, 10,11, 12-octahydro-5-methyl-5,1 1-methanobenzocyclodecen-3-ol, is also known as (—)-dezocine and Dalgan. There are three chiral carbon atoms in the molecule, so that eight stereoisomeric forms plus racemates are possible. Only two stereoisomers and a racemate have been reported.
Similarity to known substances and effects on the CNS
Dezocine has been classified pharmacologically as a partial agonist at mu opioid receptors with little affinity for kappa receptors. In rats it is approximately one-quarter as potent as
nalorphine as an opioid antagonist. In humans, it is a potent analgesic with a profile somewhat similar to that of buprenorphine. Its pharmacological actions are more easily reversed by naloxone than are those of buprenorphine. Its analgesic potency is estimated to be equal to that of morphine. Like morphine, it depresses respiration, but its action in depressing blood pressure may be less than that of morphine. Its effects on the central nervous system can be reversed by mu-receptor antagonists such as naloxone. Dezocine is rapidly distributed after intramuscular injection, with a. mean half-life of 2.5 hours. It is metabolized mainly by glucuronidation.
Dependence potential
In non-dependent drug abusers single doses of dezocine produce miosis, other opioid effects, "liking" (i.e., subjects like the effects of the drug) and euphoria. There is no evidence of dysphoric sedative and hallucinogenic effects such as those seen with pentazocine. The potential for physical dependence on dezocine has not been studied in humans, and the character, intensity and time course of withdrawal phenomena, if any, are unknown. The drug produces physical dependence in rodents but only minimal physical dependence in monkeys; it does not suppress morphine abstinence. It substitutes for codeine in animal self-administration experiments and the pattern of response is similar to that seen after buprenorphine, butorphanol and nalbuphine. In animals trained to discriminate between a mu agonist (etorphine) and a kappa agonist (ethylketazocine), dezocine was generalized to etorphine, which indicates that it acts predominantly as a mu agonist.
Actual abuse and or/evidence of likelihood of abuse
Dezocine is neither registered nor marketed in any country, but is subject to national control in five of 37 reporting countries. No cases of abuse or of illicit manufacture or traffic have been reported. Its low potential for physical dependence in animals, failure to suppress morphine withdrawal signs in monkeys, limited respiratory depressant activity and antagonist activity suggest that the abuse liability of dezocine is less than that of morphine.
Therapeutic usefulness
Dezocine is not yet available commercially. It has many of the same therapeutic indications as morphine. The Committee provisionally rated the therapeutic usefulness of dezocine as potentially moderate to high but decided to reserve giving a more definite opinion until more data become available following registration of the drug and more widespread experience with it.
Recommendation
On the basis of the available data concerning its pharmacological profile and its dependence potential in animals, and the absence of reports of actual abuse, the Committee rated the likelihood of abuse of dezocine as moderate and the therapeutic usefulness as potentially moderate to high. The degree of seriousness of the public health and social problems that might be associated with abuse of the drug was predicted to be not great enough to warrant international control at this time. However, the Committee recognized that, because of the limited experience with the drug in vulnerable populations, it will need to be carefully monitored when it enters clinical use. The Committee did not recommend scheduling of dezocine.
Dezocine (INN, CAS 53648- 55-8), chemically (-)-13-amino-5,6,7,8,9, 10,11, 12-octahydro-5-methyl-5,1 1-methanobenzocyclodecen-3-ol, is also known as (—)-dezocine and Dalgan. There are three chiral carbon atoms in the molecule, so that eight stereoisomeric forms plus racemates are possible. Only two stereoisomers and a racemate have been reported.
Similarity to known substances and effects on the CNS
Dezocine has been classified pharmacologically as a partial agonist at mu opioid receptors with little affinity for kappa receptors. In rats it is approximately one-quarter as potent as
nalorphine as an opioid antagonist. In humans, it is a potent analgesic with a profile somewhat similar to that of buprenorphine. Its pharmacological actions are more easily reversed by naloxone than are those of buprenorphine. Its analgesic potency is estimated to be equal to that of morphine. Like morphine, it depresses respiration, but its action in depressing blood pressure may be less than that of morphine. Its effects on the central nervous system can be reversed by mu-receptor antagonists such as naloxone. Dezocine is rapidly distributed after intramuscular injection, with a. mean half-life of 2.5 hours. It is metabolized mainly by glucuronidation.
Dependence potential
In non-dependent drug abusers single doses of dezocine produce miosis, other opioid effects, "liking" (i.e., subjects like the effects of the drug) and euphoria. There is no evidence of dysphoric sedative and hallucinogenic effects such as those seen with pentazocine. The potential for physical dependence on dezocine has not been studied in humans, and the character, intensity and time course of withdrawal phenomena, if any, are unknown. The drug produces physical dependence in rodents but only minimal physical dependence in monkeys; it does not suppress morphine abstinence. It substitutes for codeine in animal self-administration experiments and the pattern of response is similar to that seen after buprenorphine, butorphanol and nalbuphine. In animals trained to discriminate between a mu agonist (etorphine) and a kappa agonist (ethylketazocine), dezocine was generalized to etorphine, which indicates that it acts predominantly as a mu agonist.
Actual abuse and or/evidence of likelihood of abuse
Dezocine is neither registered nor marketed in any country, but is subject to national control in five of 37 reporting countries. No cases of abuse or of illicit manufacture or traffic have been reported. Its low potential for physical dependence in animals, failure to suppress morphine withdrawal signs in monkeys, limited respiratory depressant activity and antagonist activity suggest that the abuse liability of dezocine is less than that of morphine.
Therapeutic usefulness
Dezocine is not yet available commercially. It has many of the same therapeutic indications as morphine. The Committee provisionally rated the therapeutic usefulness of dezocine as potentially moderate to high but decided to reserve giving a more definite opinion until more data become available following registration of the drug and more widespread experience with it.
Recommendation
On the basis of the available data concerning its pharmacological profile and its dependence potential in animals, and the absence of reports of actual abuse, the Committee rated the likelihood of abuse of dezocine as moderate and the therapeutic usefulness as potentially moderate to high. The degree of seriousness of the public health and social problems that might be associated with abuse of the drug was predicted to be not great enough to warrant international control at this time. However, the Committee recognized that, because of the limited experience with the drug in vulnerable populations, it will need to be carefully monitored when it enters clinical use. The Committee did not recommend scheduling of dezocine.
ECDD Recommendation
Scheduling/control not currently recommended
Link to full TRS
who_trs_775.pdf1.98 MB