IUPAC Name
17-cyclobutylmethyl-
morphinan-3,14-diol
Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Butorphanol (INN) is chemically (–)-17-(cyclobutylmethyl)morphinan-3,14-diol.
Previous review
Butorphanol was pre-reviewed by the Committee at its thirty-third meeting in September 2002 (3). The Committee recommended a critical review based on reports of abuse in some countries.
Similarity to known substances and effects on the central nervous system
Butorphanol is a synthetic opioid partial agonist analgesic with proper- ties similar to other µ-opioid agonists such as scheduled substances buprenorphine and pentazocine. Although in radioligand-binding studies, butorphanol binds to both µ- and κ-opioid receptors, most of the observed behavioural, pharmacological and therapeutic effects appear to be due to its µ-opioid receptor agonist activity. Early studies suggested that butorphanol did not produce complete respiratory depressant effects and a "plateau" or ceiling effect" was observed although more recent studies have challenged this notion. Moderate adverse effects on the central nervous system such as nausea/vomiting, headache, clamminess, sweatiness, asthenia, paraesthe- sia, sedation, lethargy, anxiety, nervousness, euphoria, vertigo, dizziness, floating feeling, confusion and light-headedness are often reported following both parenteral and intranasal administration.
Dependence potential
Early preclinical studies in laboratory animals suggested that butorphanol has lower abuse potential than full µ-agonists such as morphine. Human studies have indicated that although the incidence of butorphanol dependence is infrequent, the withdrawal symptoms are very similar to those observed for morphine and buprenorphine. Information on the abuse potential of the different formulations of butorphanol shows that, from a pharmacological viewpoint, the trans-nasal preparation does not appear to differ in its abuse liability from the parenteral preparations. However, other non- pharmacological factors such as availability and pattern of use can play critical roles in the likelihood of its abuse.
Actual abuse and/or evidence of likelihood of abuse
Abuse and diversion have been reported by very few countries — only two countries of the 74 that responded to the WHO questionnaire mentioned abuse of butorphanol.
Therapeutic usefulness
Butorphanol is used medically in humans as an analgesic for the relief of moderate-to-severe acute pain in certain specific conditions such as post- surgical pain or migraine. Butorphanol was stated as being available for medical use in 21 of the 74 countries that responded to the WHO questionnaire. It is also used in veterinary medicine as an analgesic and antitussive agent.
Recommendation
After reviewing the information available, the Committee considered that the level of abuse of butorphanol is low, limited to a few countries and does not pose a risk to public health. Therefore, the Committee did not recommend scheduling of butorphanol.
Butorphanol (INN) is chemically (–)-17-(cyclobutylmethyl)morphinan-3,14-diol.
Previous review
Butorphanol was pre-reviewed by the Committee at its thirty-third meeting in September 2002 (3). The Committee recommended a critical review based on reports of abuse in some countries.
Similarity to known substances and effects on the central nervous system
Butorphanol is a synthetic opioid partial agonist analgesic with proper- ties similar to other µ-opioid agonists such as scheduled substances buprenorphine and pentazocine. Although in radioligand-binding studies, butorphanol binds to both µ- and κ-opioid receptors, most of the observed behavioural, pharmacological and therapeutic effects appear to be due to its µ-opioid receptor agonist activity. Early studies suggested that butorphanol did not produce complete respiratory depressant effects and a "plateau" or ceiling effect" was observed although more recent studies have challenged this notion. Moderate adverse effects on the central nervous system such as nausea/vomiting, headache, clamminess, sweatiness, asthenia, paraesthe- sia, sedation, lethargy, anxiety, nervousness, euphoria, vertigo, dizziness, floating feeling, confusion and light-headedness are often reported following both parenteral and intranasal administration.
Dependence potential
Early preclinical studies in laboratory animals suggested that butorphanol has lower abuse potential than full µ-agonists such as morphine. Human studies have indicated that although the incidence of butorphanol dependence is infrequent, the withdrawal symptoms are very similar to those observed for morphine and buprenorphine. Information on the abuse potential of the different formulations of butorphanol shows that, from a pharmacological viewpoint, the trans-nasal preparation does not appear to differ in its abuse liability from the parenteral preparations. However, other non- pharmacological factors such as availability and pattern of use can play critical roles in the likelihood of its abuse.
Actual abuse and/or evidence of likelihood of abuse
Abuse and diversion have been reported by very few countries — only two countries of the 74 that responded to the WHO questionnaire mentioned abuse of butorphanol.
Therapeutic usefulness
Butorphanol is used medically in humans as an analgesic for the relief of moderate-to-severe acute pain in certain specific conditions such as post- surgical pain or migraine. Butorphanol was stated as being available for medical use in 21 of the 74 countries that responded to the WHO questionnaire. It is also used in veterinary medicine as an analgesic and antitussive agent.
Recommendation
After reviewing the information available, the Committee considered that the level of abuse of butorphanol is low, limited to a few countries and does not pose a risk to public health. Therefore, the Committee did not recommend scheduling of butorphanol.
ECDD Recommendation
Scheduling/control not currently recommended
Link to full TRS
who_trs_942.pdf526.62 KB