Our cells are filled with intracellular and surface cell
receptors (Berg & Clarke, 2018). These receptor proteins are
delineated by structure and bind to a variety of substances responsible
for creating a reaction or lack thereof. When a ligand binds to the
appropriate receptor, signal transduction activates the receptor and
produces a biological response ( Berg & Clarke, 2018). Changes in
shape or activity after binding allow signal transmission outside the
cell or significant changes within the cell, creating an altered
chemical when binding to a ligand-gated-ion channel ( Berg & Clarke,
2018). This post will discuss the agonist/ antagonist spectrum of
psychopharmacological agents, G-proteins and ion-gated channels, and
epigenetics and their relevance to practice.
Agonists act like ligands, binding to receptors and causing action
(Berg & Clarke, 2018). Ligands or agonists consist of
pharmaceuticals, drugs, light, hormones, and nerve impulses. Ligands and
agonists jump in and out of receptors, increasing signaling or changes
in the cell. Antagonists block the standard action of ligands,
preventing a response from the receptor (Berg & Clarke, 2018).
Competitive antagonists bind to receptors and prevent ligands from
attaching to its preferred receptor, inhibiting stimulation, and leaving
the receptor unchanged (Berg & Clarke, 2018). Naloxone is a
competitive antagonist to opiate receptors London, 2017). The naloxone
has a stronger affinity for the receptor, making it more desirable. The
medication discontinues the effects of the opiates by taking their
place on the receptor. The higher the dose of opiates circulating the
more naloxone required. Due to the excess amount of continued
competition for receptors, some patients require multiple doses of
naloxone before regaining the ability to breath or regain consciousness
G-protein coupled receptors (GPCRs) target 30-50% of psychotropic
medications (Stahl, 2013). As the most abundant protein family,
GPCR ligands include neurotransmitters such as serotonin,
norepinepherine, and dopamine. After aligand binds to a GPCR, the GPCR
undergoes a conformational change (London, 2017). Alpha subunit
exchanges Guanyl nucleotide phosphates, GTP, GPP, and Alpha unit
disassociates and regulates target proteins (London, 2017). Regulation
of neurotransmission is imperative in medication management (London,
2017). The target proteins can then relay signals via a second
messenger, and GTP is finally hydrolyzed to GPP (Lambert, 2004).
G-protein receptors tend to have a delay in effect due to a requirement
for the accumulation of changed cellular function (London, 2017).
Ion gated channel linked receptors open and close in response to a
chemical message changing signal transduction in the synaptic cleft.
These ion channels act like pores in the cellular membrane to allow ion
passage (Stahl, 2013). Transmembrane ion channels open and close in
response to the binding of a ligand, differentiated by shape. The
binding will cause the channel to open or close, changing the protein
conformation of the entire structure (Berg & Clarke, 2018). When
channels open, ions like potassium, sodium, chloride, and calcium can
travel through and change the electrical process creating an
intracellular electrical response (Berg & Clarke, 2018).
Psychopharmacology relies heavily on these ion channels in medication
management. Ion-channel linked receptors act along an agonist spectrum;
medications can produce conformational changes in these receptors to
create any state of the agonist spectrum (Stahl, 2013).
The genetic material in the body is referred to as a genome (Stahl,
2013). Every cell in the body carries the same DNA but only expresses
specific genes required for its domain (Stahl, 2013). For this reason,
cells in the dermis only produce cells required to maintain and
rejuvenate the dermis. Epigenetics is the reason why skin cells differ
from brain cells or cardiac cells. Epigenetics is a term used for the
external modifications to the DNA affecting the way it is recognized by
cells (Stahl, 2013). There are thee different methods of epigenetics,
DNA myelination, histone acetylation, and microRNA (Stahl, 2013).
Genomes are affected by different exposures during development,
environmental chemicals, drugs or pharmaceuticals, aging, and diet
(Stahl, 2013). Alterations in genes may result from these exposures and
be passed on to offspring causing a change in the epigenome (Stahl,
Psychotropic medications target specific molecular sites to increase
neurotransmission. After neurotransmitters release from neurons, they
are quickly recollected and utilized again for neurotransmission (Stahl,
2013). The five essential sites of action for psychotropic medications
are 12-transmembrane-region transporter,
7-transmembrane-region-G-protein linked, enzymes,
4-transmembrane-region-ligand-gated ion channel, and
6-transmembrane-region-voltage-gated ion channels (Stahl, 2013).
When cellular alterations occur due to brain injury,
neurodegeneration, changes in the extracellular matrix, and changes in
voltage and ligand-gated ion channels transpire (Iori, 2018). A variety
of molecular changes, regulation of gene expression, and epigenetic
modifications take place as well(Iori, 2018). As a result, functional
impairments such as epilepsy, developmental delay,
cognitive/sensory-motor deficits, and drug refractoriness may
occur (Iori, 2018). Many factors affect the outcomes of medication.
Through assessment is required to determine environmental issues,
incidents of trauma, and relevant health history. Understanding that
many factors influence the effectiveness of the psychotropic medication
is imperative when determining the appropriate treatment course
Recreational drug use, in combination with prescription medication,
is critical to determine. Like antidepressants, drugs like
methylphenidate and cocaine target monoamine transporters; this
increases the risk for an oversaturation of serotonin, norepinephrine,
or dopamine in the synaptic cleft. Oversaturation can potentially cause
an issue for signal transduction in other neurotransmitters (Stahl,
2013). This oversaturation of serotonin may cause a toxic level of
serotonin, referred to as serotonin syndrome. Patients with serotonin
syndrome/toxicity present with neuromuscular, autonomic, and mental
status changes. Stopping drugs that target monoamine transporters will
help decrease levels of serotonin and should return the individual to
their normal state of health (Foong, Grindrod, Patel, & Kellar,
In conclusion, neurotransmission is the cornerstone of
psychopharmacology. Although enormously complicated, it is imperative
providers understand that small changes in cellular function, additional
drugs present in the body, and electrolyte imbalances affect
prescription medication functions and desired effects. With a shortage
of psychiatric prescribers and a mental health crisis around the world,
all healthcare providers must have a proper understanding of
psychopharmacology and interactions with other body systems.
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. https://doi.org/10.1093/ijnp/pyy071
Foong, A. L., Grindrod, K. A., Patel, T., & Kellar, J. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian family physician Medecin de famille canadien, 64(10), 720–727.
Iori, V. (2018). Epigenetic and pharmacological targeting of
neuroinflammation as novel therapeutic interventions for epilepsy.
Lambert, D. G. (2004). Drugs and receptors, Continuing Education in Anaesthesia Critical Care & Pain, 4(6), 181–184, https://doi.org/10.1093/bjaceaccp/mkh049
London, E. D. (2017). Imaging drug action in the brain. Place of publication not identified: Routledge.
Stahl, S. M. (2013). Stahl’s essential psychopharmacology:
Neuroscientific basis and practical applications (4th ed.). New York,
NY: Cambridge University Press