Foundational Neuroscience
The Agonist-To-Antagonist Spectrum of Action of Psychopharmacologic Agents
Drugs acting at a receptor occur in a spectrum from full agonist to antagonist to an inverse agonist. Agonists are drugs with affinity (bind to the target receptor) and intrinsic efficacy (alter receptor activity to produce a response). Antagonists bind to the target receptor but have no intrinsic efficacy, thus not producing a response (Berg & Clarke, 2018). A partial agonist binds and activates the receptor, but only with partial efficacy compared with endogenous and full agonists. It affects the efficacy of psychopharmacologic treatments since the intrinsic efficacy is less than that of a full agonist (Berg & Clarke, 2018). An inverse agonist binds to the receptor, hinders normal activity, and exerts the opposite pharmacological activity. Inverse agonist functionality may affect the efficacy of psychopharmacologic treatments since it oppositely activates the receptor.

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Compare and Contrast the Actions of G Couple Proteins and Ion Gated Channel
Ion-gated channels and G protein–coupled receptors (GPCRs) are two primary classes of proteins involved in membrane signaling and are drug targets. They interact with lipids in cell membranes and are regulated by lipids in their environment (Duncan et al., 2020). Ion-gated channels have an intrinsic enzymatic activity that produces an intracellular signal upon activation. On the other hand, GPCRs depend on their interaction with G proteins to convey signals to membrane-bound effectors, including ion channels and enzymes (Calebiro et al., 2021). Ion-gated channels are directly connected to ion channels and contain two functional domains, an extracellular site that binds neurotransmitters and a membrane-spanning domain that forms an ion channel. In contrast, GPCRs do not have ion channels in their structure and affect channels by activating G-protein.
Role of Epigenetics in Pharmacologic Action
Epigenetics studies DNA modifications that do not alter a person’s genetic code, though they can influence gene expression. Epigenetics can contribute to pharmacologic action by enabling researchers to understand how a disease is established and inherited. They are crucial in identifying how a disease develops and respond to pharmacologic intervention (Tomaselli et al., 2020). Many disease states have underlying epigenetic factors. This opens up a new opportunity for drug development by targeting the related mechanisms with newly established epigenetic drugs.
How This Information May Impact the Way I Prescribe Medications to Clients
The information on the agonist-to-antagonist spectrum will impact how I prescribe psychopharmacologic agents in my PMHNP practice. This includes identifying if a drug is an agonist, antagonist, partial agonist, or inverse agonist and determining the action I want a drug to produce. The PMHNP must be aware of a drug’s action when prescribing psychopharmacologic agents for depression. An agonist will suppress depression; an inverse agonist, in equivalence, will worsen depression; a partial agonist will partially alleviate depression; an antagonist will block the full and partial agonists from alleviating depression and block the inverse agonists from worsening depression. However, the antagonist will neither alleviate nor worsen depressive symptoms.  
Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The international journal of Neuropsychopharmacology, 21(10), 962–977.
Calebiro, D., Koszegi, Z., Lanoiselée, Y., Miljus, T., & O’Brien, S. (2021). G protein-coupled receptor-G protein interactions: a single-molecule perspective. Physiological Reviews, 101(3), 857–906.
Duncan, A. L., Song, W., & Sansom, M. S. (2020). Lipid-dependent regulation of ion channels and G protein–coupled receptors: insights from structures and simulations. Annual Review of Pharmacology and Toxicology, pp. 60, 31–50.
Tomaselli, D., Lucidi, A., Rotili, D., & Mai, A. (2020). Epigenetic polypharmacology: A new frontier for epi‐drug discovery. Medicinal research reviews, 40(1), 190-244.


In 1 to 2 pages write a response to each of the following:

Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments.

Compare and contrast the actions of g couple proteins and ion gated channels.

Explain how the role of epigenetics may contribute to pharmacologic action.

Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.

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