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Pathway Description
Pentazocine Opioid Antagonist Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-06-19
Last Updated: 2023-11-27
Pentazocine, the first mixed agonist-antagonist analgesic to be marketed, is an analgesic that can relieve moderate to severe pain. Pentazocine can bind as an antagonist to the mu-type opioid receptors and as an agonist of the kappa-type opioid receptor on neurons of the central nervous system (CNS). The binding of pentazocine on mu-type opioid receptors and kappa-type opioid receptors can lead to decreased levels of neuronal excitability and hyperpolarization. The preponderance of evidence suggests that pentazocine antagonizes the opioid effects by simply competing for the same receptor sites, primarily the opioid mu receptor. This drug is available as an oral tablet or as an injection (intramuscular, intravenous, or subcutaneous).
Pentazocine 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. Pentazocine 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
Pentazocine Opioid Antagonist Pathway References
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Pubmed: 16710414
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