Opioids agonist-antagonist actions, mixed

Opioid receptor binding Buprenorphine has a mixed agonistic-antagonistic action profile with a high affinity for the p-, k-, and 5-opioid receptors (Huang et al., 2001). An approximately 100-fold lower affinity was observed for the ORL1-receptor. The compound dissociates slowly from the receptor which may explain some peculiarities in its pharmacological actions. 

Christoph, T. and Buschmann, H. Zwei komplexe Wirkprinzipien in einer Struktur - Gemischte opioide Agonisten/Antagonisten und partielle Agonisten (Two complex action principles in one structure -mixed opioid agonists/antagonists and partial agonists), Pharm. i. u. Zeit 2002, 31, 40-43. 

Opioids that have mixed agonist/antagonist actions (partial agonists) induce tolerance to the agonist but not to the antagonist effects naloxone (a pure antagonist) induces no tolerance to itself. There is a cross-tolerance between opioids (for dependence and withdrawal see below). 

Pentazocine (Talwin) (see also page 252) Street Names Crackers, poor man s h oin, T s and R s> Ts and Rits (all refer to combinations w/ Ritalin) (brands Talwin, Talwin Nx [CIV]) Use Medically used as opioid analgesic euphoria similar to heroin when mixed w/antihistamines combined w/ methylphenidate (Ritalin) is new abuse combination Actions Agonist-antagonist narcotic naloxone, a narcotic antagonist added to Talwin (Talwin NX) has reduced incidence of abuse Effects Euphoria, hallucinations, skin necrosis w/ illicit injection route... 

Opioid receptor binding Nalorphine is a mixed agonist-antagonist with high affinity and low intrinsic action at the p- and K-opioid receptors. 

OPIOIDS WITH MIXED ACTIONS AGONISTS-ANTAGONISTS AND PARTIAL AGONISTS... 

Factors guiding the selection of specific opioid compounds for pain treatment include potency, pharmacokinetic characteristics, and the routes of administration available. A more potent compound could be useful when high doses of opioid are required so that the medicine can be given in a smaller volume. Duration of action also is an important consideration. In cases where a lower addiction risk is required or in patients unable to tolerate other opioids, a partial agonist or mixed agonist-antagonist compound might be a rational choice. 

---