Foundational Neuroscience comment

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An agonist to antagonist to inverse agonist spectrum

Psychoactive medications vary in how they affect activity at the synapse.  Agonists increase the neurotransmitter effect while antagonists block the neurotransmitter effect (Barron, 2018). There are gradients of how medications act creating a spectrum of influence on receptors.  Agonists can occur naturally as neurotransmitters that stimulate receptors.  Some medications also act as agonists to stimulate receptors, but medications can stimulate receptors to varying degrees (Stahl, 2013).  This creates the spectrum of how medications variably affect neurotransmitters.  The medications that stimulate receptors but do so less than full agonists are partial agonists or stabilizers.  Antagonists have no activity of their own except to block the activity of the agonists, sometimes antagonists are called silent (Stahl, 2013).  At the opposite end of the spectrum from agonists are inverse agonists. These medications block agonists and decrease activity to below the normal baseline level when there is no agonist present (Stahl, 2013).

G Couple proteins and Ion gated channels

Ion gated channels are proteins that form pores in cell membranes (Inanobe & Kurachi, 2014).  These pores are the channels that allow movement across the cell membrane and are controlled by several mechanisms. The pore may open due to the voltage difference across the membrane (Ianonobe & Kurachi, 2014).  Ligand-gated channels have a domain extracellular that associates with small chemicals and regulatory proteins (Ianonobe & Kurachi, 2014).  A domain is a protein that has its own stable structure (Genscript, 2018). Ion channels gated by ligands can be opened or closed by a neurotransmitter that is specific to a ligand binding and causing a very short, brief open active state that occurs in milliseconds (Inanobe & Kurachi, 2014).  The ligand-gated channels can also be opened when metabotropic receptors that have G protein-coupled receptors are stimulated by G protein signaling (Inanobe & Kurachi, 2014).  The G protein-coupled ion gated open response is slower and is longer lived than the neurotransmitter ion channel opening (Ianonobe & Kurachi, 2014).  In summary, an ion gated channel is a throughway to the cell and this throughway is stimulated to be opened or closed by various mechanisms.  One of the ways the ion gated channel is stimulated to open is through G couple proteins.

Epigenetics in pharmacologic action

Genes are inherited from each parent.  But epigenetics looks at if the gene is developed into its specific RNA and protein or if the gene is silenced and ignored (Stahl, 2013).  Childhood stress has been found to deactivate the receptors for glucocorticoids (Rosenfield & Ziff, 2018).  Because the receptors are deactivated people grow up with disrupted feedback.  The glucocorticoids continue to be made by the body in greater amounts because they are not detected normally.  DNA methylation occurs and creates a barrier to normal genetic codes (Rosenfield & Ziff, 2018).  Long-term effects from childhood stressors are chronic inflammation, diabetes, heart disease, obesity, schizophrenia and major depressive disorder (Rosenfield & Ziff, 2018).  Cells including neurons respond to life stressors by reacting to genetics.  Genes may be silenced or activated but the expression of genetics can vary depending on stress (Stahl, 2013).

Possible Impact on Clients

Psychopharmacology is important because of the impact interactions can have on patients.  As future prescribers, it is important to be aware of patient differences and how illness affect patient’s ability to metabolize medications (Laureate Education, 2012).  It is also important to be aware of drug interactions with other medications, foods, and metabolism.  For example, Wellbutrin is primarily metabolized by CYP2B6.  So, Wellbutrin can react with other medications that are inhibitors or inducers of CYP2B6 (, 2018).  Plavix and Ticlid are CYP2B6 inhibitors and can increase bupropion levels (, 2018).  People also metabolize medications differently.  There are four classes of metabolizers from ultra-extensive metabolizers to poor metabolizers (Barron, 2018).  Knowing the type of metabolizer that the patient is can be helpful in tailoring their medication and dosage.  Epigenetics teaches us that people with trauma can have their gene expression altered by DNA methylation.  Trauma can lead to metabolic type diseases as well as depression and schizophrenia.  As a client example, a 17-year-old male was admitted for being increasingly physically and verbally abusive to his entire foster family.  The client had pushed down a foster brother and punched and kicked his foster mom and dad.  This client had been taken away from his biological mom around age 5 due to her drug use, neglect then jail.  He was then placed with his maternal grandmother who could not handle his behavior.  The client then was placed in numerous foster homes for brief periods of time.  He acted appropriately in the Psychiatric care center, so he could control his behavior when multiple security/ authority figures were present.  The client had been on Wellbutrin at home and when he had symptoms of insomnia and aggression his Wellbutrin was increased.  He was taken off Wellbutrin and started on another medication.  Some of the more common side effects of Wellbutrin are sleep disturbance (45%), agitation (32%), irritability, and anxiety (, 2018).  This patient’s history of trauma and aggression set him up for depression, anxiety and irritability then when he had increased symptoms with the medication it was increased to the maximum dose as an outpatient.  He became increasingly agitated and then violent which led to his admission to an inpatient psychiatric facility.


Barron, S. (2018). Psychopharmacology. Nobia textbook series:  Psychology. (2018). Wellbutrin. Retrieved from

Genscript. (2018). Domain. Retrieved from

Inanobe, A., & Kurachi, Y. (2014, February). Membrane channels as integrators of G-protein mediated signaling. Biochimica et Biophysica Acta (BBA) Biomembranes1838(2), 521-531.

Laureate Education. (2012). Introduction to advanced pharmacology[Video file]. Retrieved from Walden University

Rosenfield, I., & Ziff, E. (2018). Epigenetics:  The evolution revolution. Retrieved from

Stahl, S. M. (2013). Stahl’s essential psychopharmacology:  Neuroscientific basis and practical applications (4th ed.). Retrieved from