Peer Response
Instructions:
Please read and respond to at least two of your peers' initial postings. You may want to consider the following questions in your responses to your peers:
- Compare and contrast your initial posting with those of your peers.
- How are they similar or how are they different?
- What information can you add that would help support the responses of your peers?
- Ask your peers a question for clarification about their post.
- What most interests you about their responses?
Please be sure to validate your opinions and ideas with citations and references in APA format.
Reply from Talibah Tyson
Ion Channels
The two major classes of ion channels that target drug action include ligand gated ion channels and voltage gated or voltage sensitive ion channel. Ligand gated ion channels are linked to receptors that regulate the opening and closing action of the neurotransmitter. They act as both a receptor and form an ion channel. The voltage gated or voltage sensitive ion channels opening and closing is regulated by the voltage potential or ionic charge across the membrane (Stahl, 2021.) This class of ions has voltage sensitive sodium and calcium channels that many drugs such as anticonvulsants bind to. Voltage gated ions channels are the most common drug targets (Alexander et al., 2021.)
A full agonist is characterized by the full array of downstream signal transduction which is the maximum activation of the signal transduction cascade. Antagonists block the action of the agonist by causing no change in the signal transduction. An antagonist is thought to be neutral as is has no action of its own (Stahl, 2021.) Partial antagonists are thought to be stabilizers of neurotransmission as they do not give the full amount of signal transduction. It has the capability to boost insufficient neurotransmitter activity and block any excessive activity. Inverse agonist creates a functional reduction in transducing signals opposite of the agonist.
Reference
Alexander, S. H., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Aldrich, R. W., Attali, B., Baggetta, A. M., Becirovic, E., Biel, M., Bill, R. M., Catterall, W. A.,…Zhu, M. (2021). The concise guide to pharmacology 2021/22: Ion channels. British Journal of Pharmacology, 178(S1). https://doi.org/10.1111/bph.15539Links to an external site.
Stahl, S. M. (2021). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). Cambridge University Press.
Reply from Ralph Annam
The Two Major Classes of Ion Channels
Ligand-gated ion channels (LGICs): Open upon neurotransmitter or ligand binding. Multimeric proteins (pentamers, tetramers, or trimers) are responsible for fast synaptic signaling. They often have multiple modulatory sites (e.g., GABA, NMDA, and nicotinic AChR). (Rao et al., 2022; Alexander et al., 2023).
Voltage-gated ion channels (VGICs): Open in response to membrane potential changes. The system is constructed from large subunits with voltage-sensing domains. The brain is responsible for driving action potentials, pacemaking, and muscle contraction. Represent primary drug targets for anesthetics, antiarrhythmics, and analgesics. (Jiang et al., 2022; Harris et al., 2024).
In contrast, LGICs convert chemical → electrical signals, while VGICs convert voltage → gating changes. Pharmacologically, LGICs are well suited for orthosteric/allosteric drugs, while VGICs demand state- or subtype-selective modulators.
Agonists and Related Ligands
Full agonist: Binds and produces a maximal effect (high efficacy).
Partial agonist: Causes a less than maximum effect even when all receptors are occupied; can block the effects of full agonists (for example, ar (Mohr et al., 2022).
Antagonist: Binds without changing basal activity and blocks the action of an agonist.
Inverse agonist: Opposes constitutive activity by reducing it below baseline and stabilizing inactive receptor conformations. (Qin et al., 2022; Michel et al., 2020).
Key point: Whether a ligand is an agonist, partial agonist, or antagonist depends on receptor reserve, tissue context, and constitutive activity. (Watts et al., 2023).
References
Alexander, S. P. H., et al. (2023). The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol, 180(Suppl 2), S145–S222. https://doi.org/10.1111/bph.16178
Harris, B. J., et al. (2024). Toward high-resolution modeling of small molecule–ion channel interactions. Front Pharmacol, 15, 1411428. https://doi.org/10.3389/fphar.2024.1411428
Jiang, D., et al. (2022). Structural advances in voltage-gated sodium channels. Front Pharmacol, 13, 908867. https://doi.org/10.3389/fphar.2022.908867
Mohr, P., et al. (2022). Dopamine receptor partial agonists: Do they differ in clinical efficacy? Front Psychiatry, 12, 781946. https://doi.org/10.3389/fpsyt.2021.781946
Qin, J., et al. (2022). Molecular mechanism of agonism and inverse agonism in ghrelin receptor. Nat Commun, 13, 300. https://doi.org/10.1038/s41467-022-27975-9
Rao, R., et al. (2022). Ligand-gated ion channels as therapeutic targets. Front Physiol, 13, 839437. https://doi.org/10.3389/fphys.2022.839437
Watts, S. W., et al. (2023). Receptor theory and hypertension therapy. Am J Hypertens, 37(4), 248–260. https://doi.org/10.1093/ajh/hpad121
Michel, M. C., et al. (2020). Inverse agonism at adrenoceptor subtypes. Cells, 9(9), 1923. https://doi.org/10.3390/cells9091923
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