Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Meptazinol (INN, CAS 54340-58-8), chemically m-(3-ethylhexahydro-1-methyl-1 H-azepin-3-yl)phenol, is also known as Meptid. There is one chiral carbon atom in the molecule, so that two stereoisomers and one racemate are possible.
Similarity to known substances and effects on the CNS
Meptazinol is a centrally acting agonist—antagonist opioid. Its pharmacological profile in both animals and humans is consistent with a drug whose action is predominantly mediated through the mu receptors. It is claimed that the analgesic effect of meptazinol is primarily supraspinal, and that such analgesia is associated with low levels of respiratory depression and sedation. The drug also has anticholinesterase activity. The most frequently reported adverse effects have been nausea, vomiting, dizziness, diarrhoea, sweating and hypotension. Some of these may be related to meptazinol’s anticholinesterase activity which, at higher doses, could produce the kind of toxic effects that are associated with cholinesterase inhibitors. Oral administration of meptazinol to healthy subjects results in rapid absorption and peak plasma concentrations are reached within 0.5—2 hours; intramuscular injections produce peak plasma levels within 30 minutes.
Dependence potential
Following chronic administration, abrupt withdrawal of meptazinol produced minimal withdrawal signs in rhesus monkeys; naloxone also precipitated only slight withdrawal signs in these
animals. Meptazinol failed to substitute for morphine in morphinedependent and withdrawn animals. In self-administration studies of meptazinol in rhesus monkeys, response rates for all doses of meptazinol were significantly lower than for codeine. In a drugdiscrimination study, meptazinol was generalized to the prototypic kappa agonist ethylketazocine in rhesus monkeys. It was also generalized to the prototypic mu agonist etorphine at some doses. Meptazinol does not suppress opioid withdrawal signs and symptoms in human subjects dependent on morphine; administered to methadone-maintained patients, it provokes a mild to moderate opioid withdrawal syndrome in about half of them. In nondependent heroin abusers, doses in the therapeutic range are identified as having mild morphine-like effects, and produce limited "liking" and some dysphoria; higher doses do not increase scores on
a euphoria or sedation scale but do increase scores on a dysphoria scale.
Actual abuse and or/evidence of likelihood of abuse
Meptazinol is registered in 23 countries but is reported to be available for medical use in only a few. No cases of abuse have been reported. There is no evidence of illicit trafficking or manufacture.
Therapeutic usefulness
Meptazinol is reported to be a useful analgesic for the treatment of postoperative, obstetric. and chronic pain. It has been reported to produce less respiratory depression and sedation than prototypic mu agonists and other opioid agonist—antagonists, but to have certain side-effects that may be associated with its cholinomimetic actions.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and actual abuse, the Committee rated the likelihood of abuse of meptazinol as moderate and the therapeutic usefulness as moderate to high. The degree of seriousness of the public health and social problems that might be associated with the abuse of the drug was predicted to be not great enough to warrant international control at this time. The Committee did not recommend scheduling of meptazinol.
Meptazinol (INN, CAS 54340-58-8), chemically m-(3-ethylhexahydro-1-methyl-1 H-azepin-3-yl)phenol, is also known as Meptid. There is one chiral carbon atom in the molecule, so that two stereoisomers and one racemate are possible.
Similarity to known substances and effects on the CNS
Meptazinol is a centrally acting agonist—antagonist opioid. Its pharmacological profile in both animals and humans is consistent with a drug whose action is predominantly mediated through the mu receptors. It is claimed that the analgesic effect of meptazinol is primarily supraspinal, and that such analgesia is associated with low levels of respiratory depression and sedation. The drug also has anticholinesterase activity. The most frequently reported adverse effects have been nausea, vomiting, dizziness, diarrhoea, sweating and hypotension. Some of these may be related to meptazinol’s anticholinesterase activity which, at higher doses, could produce the kind of toxic effects that are associated with cholinesterase inhibitors. Oral administration of meptazinol to healthy subjects results in rapid absorption and peak plasma concentrations are reached within 0.5—2 hours; intramuscular injections produce peak plasma levels within 30 minutes.
Dependence potential
Following chronic administration, abrupt withdrawal of meptazinol produced minimal withdrawal signs in rhesus monkeys; naloxone also precipitated only slight withdrawal signs in these
animals. Meptazinol failed to substitute for morphine in morphinedependent and withdrawn animals. In self-administration studies of meptazinol in rhesus monkeys, response rates for all doses of meptazinol were significantly lower than for codeine. In a drugdiscrimination study, meptazinol was generalized to the prototypic kappa agonist ethylketazocine in rhesus monkeys. It was also generalized to the prototypic mu agonist etorphine at some doses. Meptazinol does not suppress opioid withdrawal signs and symptoms in human subjects dependent on morphine; administered to methadone-maintained patients, it provokes a mild to moderate opioid withdrawal syndrome in about half of them. In nondependent heroin abusers, doses in the therapeutic range are identified as having mild morphine-like effects, and produce limited "liking" and some dysphoria; higher doses do not increase scores on
a euphoria or sedation scale but do increase scores on a dysphoria scale.
Actual abuse and or/evidence of likelihood of abuse
Meptazinol is registered in 23 countries but is reported to be available for medical use in only a few. No cases of abuse have been reported. There is no evidence of illicit trafficking or manufacture.
Therapeutic usefulness
Meptazinol is reported to be a useful analgesic for the treatment of postoperative, obstetric. and chronic pain. It has been reported to produce less respiratory depression and sedation than prototypic mu agonists and other opioid agonist—antagonists, but to have certain side-effects that may be associated with its cholinomimetic actions.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and actual abuse, the Committee rated the likelihood of abuse of meptazinol as moderate and the therapeutic usefulness as moderate to high. The degree of seriousness of the public health and social problems that might be associated with the abuse of the drug was predicted to be not great enough to warrant international control at this time. The Committee did not recommend scheduling of meptazinol.
ECDD Recommendation
Scheduling/control not currently recommended
Link to full TRS
who_trs_775.pdf1.98 MB