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Pathway Description
Nalbuphine Opioid Antagonist Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-06-19
Last Updated: 2023-11-27
Nalbuphine, also known as Rubuphine and Nubain, is a synthetic opioid agonist-antagonist. This drug is thus an analgesic used to treat pain, for pre and postoperative analgesia, and for analgesia in labor and delivery (moderate to severe pain). This narcotic is an agonist to kappa-opioid receptors and an antagonist or partial agonist at mu-opioid receptors in the central nervous system (CNS) (probably in or associated with the limbic system). The binding of nalbuphine can prevent the effects caused by endogenous opioids, which antagonizes the impact of opiates such as respiratory depression or drug craving. Nalbuphine's analgesic potency is equivalent to morphine on a milligram basis. Symptoms of overdose include primarily sleepiness and mild dysphoria. Nalbuphine is administered as an intramuscular/intravenous/subcutaneous injections.
Nalbuphine inhibits the exchange of GTP for GDP which is required to activate the G-protein complex. This prevents the Gi subunit of the mu opioid receptor from inhibiting adenylate cyclase, which can therefore continue to catalyze ATP into cAMP. cAMP increases the excitability in spinal cord pain transmission neurons which allows the patient to feel pain rather than the analgesic effects of opioids. The inhibition of Mu-type opioid receptors also prevents the Gi subunit of the mu opioid receptor from activating the inwardly rectifying potassium channel increasing K+ conductance which would cause hyperpolarization. Nalbuphine also prevents the gamma subunit of the mu opioid receptor from inhibiting the N-type calcium channels on the neuron. This allows calcium to enter the neuron and depolarize. The inhibition of mu-opioid receptors prevents hyperpolarization in the neuron, allowing it to fire at a normal rate. The neuron is able to depolarize and the high concentration of calcium releases GABA into the synapse which binds to GABA receptors. GABA receptors inhibits dopamine cell firing in the pain transmission neurons. This prevents the analgesic and depressive effects of opioids, preventing opioid overdose. GABA also inhibits dopamine cell firing in the reward pathway which is the main cause of addiction to opioids and other drugs.
References
Nalbuphine Opioid Antagonist Pathway References
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Pubmed: 16710414
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