Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Zipeprol (CAS 34758-83-3), chemically a-(a-methoxybenzyl)-4-(Bmethoxyphenethyl)-1-piperazineethanol, is also known as Antituxil-Z, Cerm-3024, Chilvax, Delaviral, Dovavixin, Jactus, Eritos, Mirsol, Ogyline, Respilene, Respirase, Respirex, Sanotus, Santus, Silentos, Sousibim, Talasa, Tusigen, Tussiflex and Zitoxil. Zipeprol has three asymmetric carbon atoms, so eight stereoisomeric forms are possible.
WHO review history
Zipeprol was pre-reviewed by the 28th meeting (6) of the Committee in 1992, which recommended it for critical review.
Similarity to known substances and effects on the CNS
In laboratory animals, zipeprol has been shown to have an antitussive activity weaker than codeine and comparable to dextromethorphan. Its pharmacological properties are different from those of opioid antitussives, such as codeine, in that zipeprol has anticholinergic activities. It also does not produce respiratory depression, bile duct constriction or constipation, which are often associated with narcotic antitussives. Unlike opioids, zipeprol is essentially devoid of analgesic activity, but at high doses, zipeprol acts as a weak opioid agonist. Also, unlike opioids zipeprol shows a bi-phasic effect in competing for binding sites in rat brain homogenates.
Dependence potential
In rats, low doses of zipeprol amplify some opioid withdrawal manifestations whereas high doses suppress some symptoms. Zipeprol is assessed to have a moderate dependence potential.
Actual abuse and or/evidence of likelihood of abuse
There have been a number of reports on the abuse of zipeprol from Brazil, Chile, France, Italy, Mexico, the Republic of Korea, Switzerland and the former Yugoslavia. These reports suggest that its sedative, hallucinatory and euphorigenic effects, and its ability to suppress some signs of opioid withdrawal at high doses, may be the reasons for its abuse. Over-the counter distribution of zipeprol preparations may have contributed to its widespread abuse in some places. In view of this, zipeprol is assessed to have a moderate abuse liability. Adverse health consequences of zipeprol abuse include seizures, hallucinations, confusion and amnesia. Dose escalation is not uncommon, and fatal cases from acute intoxication have been reported from several countries. The tablet form of zipeprol has been used for intravenous administration.
Therapeutic usefulness
A number of clinical studies have demonstrated the therapeutic efficacy of zipeprol for the treatment of cough. The therapeutic usefulness of zipeprol is assessed to be between little and moderate.
Recommendation
Although zipeprol is a weak opioid agonist at high doses, its toxicity, hallucinogenic and other psychotropic effects constitute a significant element in its abuse. It is therefore appropriate to consider its control under the Convention on Psychotropic Substances, 1971. On the basis of the available data concerning its pharmacological and toxicological profile, dependence potential and likelihood of abuse, the public health and social problems associated with the abuse of zipeprol are assessed to be substantial. On the basis of this and the assessment of its therapeutic usefulness, it is recommended that zipeprol be placed in Schedule II of the Convention on Psychotropic Substances, 1971.
Zipeprol (CAS 34758-83-3), chemically a-(a-methoxybenzyl)-4-(Bmethoxyphenethyl)-1-piperazineethanol, is also known as Antituxil-Z, Cerm-3024, Chilvax, Delaviral, Dovavixin, Jactus, Eritos, Mirsol, Ogyline, Respilene, Respirase, Respirex, Sanotus, Santus, Silentos, Sousibim, Talasa, Tusigen, Tussiflex and Zitoxil. Zipeprol has three asymmetric carbon atoms, so eight stereoisomeric forms are possible.
WHO review history
Zipeprol was pre-reviewed by the 28th meeting (6) of the Committee in 1992, which recommended it for critical review.
Similarity to known substances and effects on the CNS
In laboratory animals, zipeprol has been shown to have an antitussive activity weaker than codeine and comparable to dextromethorphan. Its pharmacological properties are different from those of opioid antitussives, such as codeine, in that zipeprol has anticholinergic activities. It also does not produce respiratory depression, bile duct constriction or constipation, which are often associated with narcotic antitussives. Unlike opioids, zipeprol is essentially devoid of analgesic activity, but at high doses, zipeprol acts as a weak opioid agonist. Also, unlike opioids zipeprol shows a bi-phasic effect in competing for binding sites in rat brain homogenates.
Dependence potential
In rats, low doses of zipeprol amplify some opioid withdrawal manifestations whereas high doses suppress some symptoms. Zipeprol is assessed to have a moderate dependence potential.
Actual abuse and or/evidence of likelihood of abuse
There have been a number of reports on the abuse of zipeprol from Brazil, Chile, France, Italy, Mexico, the Republic of Korea, Switzerland and the former Yugoslavia. These reports suggest that its sedative, hallucinatory and euphorigenic effects, and its ability to suppress some signs of opioid withdrawal at high doses, may be the reasons for its abuse. Over-the counter distribution of zipeprol preparations may have contributed to its widespread abuse in some places. In view of this, zipeprol is assessed to have a moderate abuse liability. Adverse health consequences of zipeprol abuse include seizures, hallucinations, confusion and amnesia. Dose escalation is not uncommon, and fatal cases from acute intoxication have been reported from several countries. The tablet form of zipeprol has been used for intravenous administration.
Therapeutic usefulness
A number of clinical studies have demonstrated the therapeutic efficacy of zipeprol for the treatment of cough. The therapeutic usefulness of zipeprol is assessed to be between little and moderate.
Recommendation
Although zipeprol is a weak opioid agonist at high doses, its toxicity, hallucinogenic and other psychotropic effects constitute a significant element in its abuse. It is therefore appropriate to consider its control under the Convention on Psychotropic Substances, 1971. On the basis of the available data concerning its pharmacological and toxicological profile, dependence potential and likelihood of abuse, the public health and social problems associated with the abuse of zipeprol are assessed to be substantial. On the basis of this and the assessment of its therapeutic usefulness, it is recommended that zipeprol be placed in Schedule II of the Convention on Psychotropic Substances, 1971.
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_856.pdf1.07 MB