Nalbuphine, structure

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

Nalbuphine is structurally related to both naloxone and oxymorphone. It is an agonist-antagonist opioid possessing a spectrum of effects that resemble those of pentazocine however, nalbuphine is a more potent antagonist at p receptors and is less likely to produce dysphoria than is pentazocine. 

Nalbuphine is a partial opioid agonist structurally similar to naloxone. Like naloxone it is an antagonist at OPs) ) receptors, whilst achieving analgesia via an agonist effect at OP2(k) receptors. 

Figure 7.16. C-ring derivatives of morphine. Structures of hydromorphone (5) and oxycodone (6) from Fig. 7.1 are included for comparison. Nalmefene (64) is an antagonist, TRK-820 (65) is a K-selective agonist, and nalbuphine (66) is a mixed agonist/antagonist.

Fig. 7 Structures of nalbuphine (22), naltrexone (23), naloxone (24), and twin drugs 25-27...

The structural similarity of nalbuphine to naltrexone could not be greater, yet the latter exhibits no analgesia. The reason for this still awaits an explanation. 

Nalbuphine is a semi-synthetic agonist-antagonist 150 opioid of the phenanthrene series. It is structurally similar to, and chemically related to, both the potent... 

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