Foundational Neuroscience: Neurotransmitters and Receptor Theory NURS 6630
Neurotransmitters and Receptor Theory
Neurotransmitters mediate the transmission of electrical impulses from one neuron to another. Multiple neurotransmitters are involved in central nervous system function, including amines (catecholamines, acetylcholine, and serotonin), amino acids (GABA, aspartate, and glutamate), peptides (neuropeptide Y), and gases such as nitric oxide (Sheffler et al., 2022). As discussed further, psychopharmacologic medications bind to specific neurotransmitter receptors, either activating (agonistic) or inhibiting (antagonistic).
Agonist-to-Antagonist Spectrum of Action of Psychopharmacologic Agents
Psychopharmacologic agents are useful in the treatment of a variety of psychiatric disorders, including mood disorders, trauma and stressor disorders, behavioral disorders, and psychotic disorders. The drugs exhibit either agonistic or antagonistic activity when acting at the receptor site.
Whereas agonists bind to and activate a receptor to produce specific actions, antagonists bind to and block specific actions or responses (Katzung, 2018; Stern et al., 2015). The dopamine hypothesis, for example, is widely accepted in the etiology of schizophrenia. Excessive dopaminergic transmission is thought to be responsible for schizophrenic symptoms, and research has found higher levels of dopaminergic receptors in schizophrenic patients (Stahl, 2018).
This epiphany is why psychopharmacologic agents that block Dopamine receptors, such as chlorpromazine, are used to treat schizophrenia. In contrast, neurodegenerative disease such as Parkinson’s Disease (PD) has been linked to decreased dopamine levels and receptors, which is why dopamine agonists such as Levodopa are used to treat it.
Partial agonists bind to and activate receptors but have only partial efficacy. Partial agonists exhibit both agonistic and antagonistic actions, for example, Buspirone, which is a partial agonist for 5HTA1 receptors and an antagonist for D2 receptors (Katzung, 2018).
As a result, Buspirone can be used as both an anxiolytic and an antidepressant medication. Conversely, inverse agonists bind to receptors to produce effects opposite to those of the agonist (Katzung, 2018). Naltrexone is an example of a partial inverse agonist that is used to treat opioid addiction.
G-coupled Proteins and Ion-gated Channels
G-coupled proteins and Ion-gated chandelles are both cell surface receptors. To release ions, ligand-gated ion channels are controlled by neurotransmitters, whereas G-coupled receptors are entirely dependent on the second messenger system (Miller & Lappin, 2022). Because of the differences in stimulation mechanisms, the receptors take varying amounts of time to activate. While ligand-gated ion channels are activated in milliseconds, G-coupled protein receptors take seconds (Miller & Lappin, 2022).
Furthermore, nicotinic acetylcholine receptors and GABA A receptors are examples of ligand-gated ion channels, whereas G-coupled receptors include muscarinic acetylcholine receptors and adrenoceptors (Katzung, 2018; Miller & Lappin, 2020). Regardless of the differences, receptors are critical in carrying out physiologic functions at the molecular level.
Role of Epigenetics in Pharmacologic Action
Genes play an essential role in the body, but so do the behaviors and environment. Epigenetics is the study of how behavior and environment influence gene expression (CDC, 2022). Unlike genetic changes, epigenetic changes are reversible and alter how the body reads the DNA sequence rather than changing the DNA sequence itself. The epigenetic changes may influence the pharmacology of certain drugs.
Brain-Derived Neurotrophic Factor (BDNF), for example, promotes neuronal survival and synaptic plasticity and is involved in learning, memory, and neurotransmitter release (Webb et al., 2020). BDNF has been shown to be expressed differently across brain regions depending on environmental stressors, ushering in the concept of epigenetics.
Human studies show that BDNF brain levels decrease in untreated major depressive illness and increase with antidepressant treatment (Webb et al., 2020). As a result, BDNF has emerged as a viable candidate for predicting response to antidepressant therapy.
Significance of the Information
Information regarding the pharmacology of drugs is critical in healthcare. In addition to understanding disease mechanisms, psychiatric mental health nurse practitioners (PMHNP) must be proficient in drug pharmacology knowledge. For example, in the etiology of PD, the PMHNP is aware of the link between the disease and Dopamine. As a result, a PMHNP may decide to prescribe a Dopamine agonist, such as Levodopa, rather than a Dopamine antagonist, which would worsen the symptoms.
Additionally, the pharmacology of a drug allows PMHNPs to understand the potential side effects of a drug. In the treatment of schizophrenia, for example, 12.5-50 mg of Risperidone may be injected into the deltoid or gluteal muscle every two weeks (McNeil et al., 2022), and a nurse should be aware that it is capable of causing extrapyramidal side effects, so the treatment should be used with caution. The information thus improves the way nurses perform their duties, resulting in better patient outcomes.
Conclusion
It is imperative for a PMHNP to have a concrete background in neuroscience. Understanding the pathophysiology of the disease is important in treating psychiatric patients, but knowledge of the medications used to treat the conditions is far more important. This enables PMHNPs to practice competently and with full practice authority, even in the absence of a supervising psychiatrist consultant. While the subject of foundational neuroscience can be difficult to grasp, interacting with colleagues and patients broadens one’s understanding and alleviates the agony of trying to decipher difficult concepts.
References
- CDC. (2022, August 15). What is epigenetics? Centers for Disease Control and Prevention. https://www.cdc.gov/genomics/disease/epigenetics.htm
- Katzung, B. G. (2018). Basic & Clinical Pharmacology. Basic & Clinical Pharmacology.
- McNeil, S. E., Gibbons, J. R., & Cogburn, M. (2022). Risperidone. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459313/
- Miller, E. J., & Lappin, S. L. (2022). Physiology, Cellular Receptor. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554403/
- Sheffler, Z. M., Reddy, V., & Pillarisetty, L. S. (2022). Physiology, Neurotransmitters. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539894/
- Stahl, S. M. (2018). Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. CNS Spectrums, 23(3), 187–191. https://doi.org/10.1017/S1092852918001013
- Stern, T. A., Fava, M., Wilens, T. E., & Rosenbaum, J. F. (2015). Massachusetts general hospital psychopharmacology and neurotherapeutics. Elsevier Health Sciences.
- Webb, L. M., Phillips, K. E., Ho, M. C., Veldic, M., & Blacker, C. J. (2020). The relationship between DNA methylation and antidepressant medications: A systematic review. International Journal of Molecular Sciences, 21(3), 826. https://doi.org/10.3390/ijms21030826
NURS 6630 Week 2 Discussion Instructions
NURS 6630 Module 2 Week 2: Neurotransmitters and Receptor Theory
Receptors and neurotransmitters are like a lock-and-key system. Just as it takes the right key to open a specific lock, it takes the right neurotransmitter to bind to a specific receptor. Not surprisingly, as it concerns psychopharmacology, the pharmacotherapeutics that are prescribed must trigger the release of certain neurotransmitters that bind to the correct receptors in order to elicit a favorable response for the patient. The mechanism of this binding and the response that follows reflects receptor theory and lies at the foundation of pharmacology.
This week, you will continue your examination of neuroanatomy and neuroscience as you engage with you colleagues in a Discussion. You will also explore the potential impacts of foundational neuroscience on the prescription of pharmacotherapeutics.
Discussion: Foundational Neuroscience
As a psychiatric and mental health nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat patients, you must not only understand the pathophysiology of psychiatric disorders but also how medications for these disorders impact the central nervous system. These concepts of foundational neuroscience can be challenging to understand. Therefore, this Discussion is designed to encourage you to think through these concepts, develop a rationale for your thinking, and deepen your understanding by interacting with your colleagues.
For this Discussion, review the Learning Resources and reflect on the concepts of foundational neuroscience as they might apply to your role as the psychiatric mental health nurse practitioner in prescribing medications for patients.
Agonist-to-antagonist Spectrum of Psychopharmacologic Agents Example Paper
An agonist is a drug or molecule that binds to and activates its specific receptor to produce a desired biological response. Endogenous agonists are those synthesized within the body, whereas exogenous agonists are from external sources and include various medications that mimic the actions of the endogenous agonists. Agonists can be classified into various categories, namely full agonists, partial agonists, and inverse agonists, depending on the intrinsic efficacy.
A full agonist has high intrinsic efficacy and thus produces maximal receptor activation with a resultant maximal intended response. A partial agonist has relatively lower intrinsic efficacy and thus produces sub-maximal receptor activation and resultant weaker biologic response. An inverse agonist, despite binding the same receptor site as the agonist, has a negative intrinsic efficacy in that it produces a biologic response that is antagonistic or opposite to that of the agonist (Berg & Clarke, 2018).
In contrast to an agonist, an antagonist does not have any intrinsic efficacy but has an affinity to receptors and acts to inhibit the effects of agonists. The agonist-to-antagonist spectrum has implications on the choice of psychopharmacological agents depending on the drug’s intrinsic activity and affinity, which translates to the desired therapeutic effect.
Comparison Of G Couple Proteins And Ion Gated Channels
G protein-coupled receptors (GPCRs) and ion gated channels (IGCs) are receptors that usually mediate cellular responses through the activation by stimuli. GPRCs function through second messenger systems and are more abundant compared to IGCs. Ligand-binding activation causes these receptors to bind to G-proteins, which facilitate the exchange of GTP for GDP, leading to a cascade of activities that cause a cellular response (Weis et al., 2018).
IGCs are trans-membrane proteins with a central pore that opens and close to control the movement of ions across the cell membrane (Phillips et al., 2020). Generally, response to a signal is slower in GPCRs due to the coupling and is activated by slower neurotransmitters such as serotonin. IGCs are activated by faster neurotransmitters such as acetylcholine, translating to a quicker response.
Role Of Epigenetics In Pharmacologic Action
Epigenetics is increasingly being adopted in the development of therapeutic pharmacological agents. Epigenetics is whereby DNA transcription is regulated through DNA methylation or histone modification without inflicting any changes to the DNA sequence (Kringel et al., 2021). This results in increased or decreased transcription of the target genes or exposure of desired parts of the DNA through conformational changes to transcription factors.
Drugs can thus be developed to target certain genes that contribute to the etiology of various diseases, including psychiatric illnesses. However, the efficacy of these therapeutic epigenetic pharmacologic agents and expected responses may depend on the presence or alteration of the target genes among individuals; thus, variability is expected in such instances.
Impact Of The Above Information On Prescription Of Medications To Patients
In light of the above information, it is important to know the genetic background of an individual before treatment. This is because certain genes are heritable, most commonly encountered within the hospital setting as a positive family history of a certain illness. It is thus important to obtain a comprehensive medical and family history before treatment. Genetic testing should also be considered, especially with several treatment failures. Genetic and environmental factors influence epigenetics; thus, it is important for medical professionals to understand this. For example, similar illnesses in twins may not respond similarly to treatment hence the need to individualize care.
References
- Berg, K., & Clarke, W. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. International Journal Of Neuropsychopharmacology, 21(10), 962-977. https://doi.org/10.1093/ijnp/pyy071
- Kringel, D., Malkusch, S., & Lötsch, J. (2021). Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis. International Journal Of Molecular Sciences, 22(14), 7250. https://doi.org/10.3390/ijms22147250
- Phillips, M., Nigam, A., & Johnson, J. (2020). The interplay between Gating and Block of Ligand-Gated Ion Channels. Brain Sciences, 10(12), 928. https://doi.org/10.3390/brainsci10120928
- Weis, W. I., & Kobilka, B. K. (2018). The Molecular Basis of G Protein-Coupled Receptor Activation. Annual Review of Biochemistry, 87, 897–919. https://doi.org/10.1146/annurev-biochem-060614-033910
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