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.    

Agonists are ligands that bind to receptors and alter or modify the state of the receptors in such a way it triggers a biological response, whereas antagonist are alpha or beta blocker ligands that refrain from or dampen a biological reaction but blocks the presenting receptors. A full agonist has the capability of producing maximal response of the target system. As the receptor stimulus invoked by an agonist maximizes its response capability as a full agonist in such system.

Partial agonists bind to and activate the presenting receptors; however, they do not have the ability to induce maximal intrinsic activity capable of producing full agonists even at full receptor occupancy and high concentration because of their low maximal efficacy when compared to the maximal efficacy of full agonists. When these partial agonists compete for the same receptors with full agonists they act as antagonists. Unless the partial agonists bind to the receptors in some sort of irreversible manner, it could be potentially be displaced from the receptor by a sufficiently high concentration of full agonist. In view of this, the efficacy of the full agonist is not affected, but its potency is reduced. Conversely, inverse agonists bind to receptors and reduce fraction of them in an active conformation. It could potentially decrease the available fraction of active receptors by binding to receptors in their inactive state preferentially, thus reducing the total possible pool of receptors in the system. In other words, an inverse agonist’s oppositional activity could be significantly reduced by competitive neutral antagonists that also bind the receptors but do nothing with them once they are attached (Camprodon and Roffman, 2016).

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

Neurotransmitter receptors such as acetylcholine that are ligand-gated ion channels have the tendency to mediate rapid postsynaptic responses while G protein – coupled neurotransmitter receptors such as serotonin and dopamine have the tendency to mediate slow postsynaptic responses. More so, a G protein-coupled receptor consist of a single polypeptide that is threaded over membrane, while ion channels comprise of pores that open and close upon ligand binding.

G protein coupled receptors interact with a variety of proteins for intracellular response, while ion channels regulate flow of ions.  Finally, G protein involves GTP (Guanosine Triphosphate) whereas ion channels do not involve GTP.

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

The drug metabolism, as a biochemical process, requires modification of pharmaceutical substances through specialized enzymatic systems. Epigenetic regulation of drug-metabolizing enzyme genes has been shown to be a significant mechanism of changes in the expression of those drug-metabolizing enzymes.  In other words, Drug absorption, distribution, metabolism, and excretion are critical processes to be considered when developing safe drugs. These identified processes are mediated by drug-metabolizing enzymes such as cytochrome P450 and transporters such as ATP-binding cassettes that are expressed in various tissues of the body such as the small intestine, liver, and kidney. These processes could potentially inhibit, limit, or enhance the systemic and target organ exposure to xenobiotics (Camprodon and Roffman, 2016). Drug-metabolizing enzymes such as cytochrome P450 isoforms are responsible for the metabolic elimination of drugs, and membrane transporters such as ATP-binding cassette transporters can affect drug absorption, distribution, and excretion processes. More so, the interplay of these drug-metabolizing enzymes and transporters could potentially determine the pharmacokinetic properties of a drug in areas of bioavailability, volume of distribution, and half-life, as well as understanding the regulation of drug-metabolizing enzymes and transporters are critical to the prediction of consequent pharmacological and toxicological effects.