Effect of Naltrexone
Current treatment of opioid dependence now involves the use of Naltrexone; a medicine related to Naloxone which is also involved in the treatment of opioid dependence. Taken orally, Naltrexone is an antagonist, or inhibitor, to the kappa opioid receptor that is active in both alcohol dependence and opioid dependence. Naltrexone interacts with KOR by being a competitive agonist which binds directly to KOR without activating it. This then prevents the binding of other endogenous ligands from activating the heterotrimeric complex (G-protein coupled receptor), preventing G-proteins, Gαi and Gβγ from disassociating and activating the cyclin dependent kinases in the signaling pathway. Furthermore, Naltrexone’s presence in the KOR also prevents the binding of ligands associated with MAPK/arrestin pathway preventing long-term opioid associated effects within neurons.
- Naltrexone's Structure
Naltrexone's Pathways
Effect of Naltrexone on Body
Naltrexone’s effect on human neuron cells starts with how it interacts with the kappa opioid receptor (KOR). By targeting the feelings associated with opioids, Naltrexone can reduce and even remove the ‘high’ that one might receive from opioids depending on one’s genetic makeup. This then disrupts the positive reinforcement that one might get from using opioids, preventing them from later becoming dependent. However, Naltrexone is not a universal fix for opioid dependence. As previously mentioned, the effectiveness of Naltrexone is genetically determined. In some cases, a patient may only feel a reduced ‘high’ from the drug or possibly experience minimal/no reduction at all. This is evidently considered to be expected due to the KOR being transcribed from the OPRK1 gene. 
-Agonist v. Antagonists
Effectiveness of Naltrexone
In addition, research shows that Naltrexone could be effective at shutting down both long-term and short-term opioid effects in neurons by blocking both signaling cascades associated with opioid dependence (MAPK and short-term). Naltrexone does this because in the KOR, different ligands are shown to result in different signaling cascades. Naltrexone, by occupying the KOR, blocks both signaling pathways without differentiation preventing any extracellular opioid signals from reaching the cell and creating an intracellular response in neuron cells.
Signal Transduction in Neurons
Viability of Naltrexone
Naltrexone’s viability over other drugs like AZ-MTAB, which can also inhibit kappa opioid receptors before ligands reach the KOR lies in its practicality, effectiveness, and safety. Naltrexone, as previously mentioned is an orally taken drug making it more practical over other drugs on the market currently being used for reducing opioid dependence. In addition, Naltrexone, acting upon the KOR’s various signaling pathways, can act as a general treatment option that is effective across multiple regions of intracellular activity which are associated with opioid dependence. Lastly, Naltrexone is also one of the more researched options available on the market and has been clinically found to be viable by the FDA for the reduction of opioids unlike AZ-MTAB, which has only been tested in mice.
KOR Signaling Pathways Connection to MAPK signaling
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