What receptor do agonists target?

From the Guidelines

Agonists target the mu opioid receptor (MOR) to produce their therapeutic effects, particularly in the management of pain. The analgesic effects of opioid medications are predominantly mediated through agonist effects at MORs, although for some compounds, their binding to delta and kappa opioid receptors also contributes to analgesic effects 1. This is supported by the fact that brain regions that regulate pain perception contain high MOR levels, which explains why opioid medications can be so effective in the management of severe acute pain 1.

The specificity of an agonist for its target receptor determines both its therapeutic effects and potential side effects. For example, morphine is a mu-opioid receptor agonist used for pain management, and its binding to MORs triggers a biological response that produces analgesia 1. The strength of receptor binding (affinity) and the degree of receptor activation (efficacy) determine how potent an agonist will be in producing its biological effects.

Some agonists, such as GLP-1 receptor agonists, target specific receptors in the body to produce therapeutic effects, including reducing albuminuria and slowing eGFR decline in patients with chronic kidney disease 1. These agonists have shown cardiovascular and CKD benefits, and are preferred agents in the management of type 2 diabetes mellitus and obesity 1.

In summary, agonists target specific receptors, such as the mu opioid receptor, to produce their therapeutic effects, and the specificity of an agonist for its target receptor determines both its therapeutic effects and potential side effects. The most recent and highest quality study supporting this is from 2021, which highlights the importance of mu opioid receptors in the analgesic effects of opioid medications 1.

From the FDA Drug Label

Morphine, a full opioid agonist, is relatively selective for the mu receptor, although it can interact with other opioid receptors at higher doses Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses

Main Receptor Targeted by Agonists:

• Mu receptor: The primary receptor targeted by morphine, a full opioid agonist.
• Other opioid receptors: May be interacted with at higher doses.

2, 2, 3

From the Research

Receptor Targets for Agonists

• Agonists target G protein-coupled receptors (GPCRs), the largest family of human membrane proteins and an important class of drug targets 4, 5, 6, 7, 8
• GPCRs play a role in maintaining numerous physiological processes, and agonist or antagonist, orthosteric effects or allosteric effects, and biased signaling or balanced signaling characterize the complexity of GPCR dynamic features 4
• Approximately 35% of approved drugs target GPCRs, implying that GPCRs constitute the largest family of proteins targeted by approved drugs 5
• GPCRs are involved in various cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development, and apoptosis, making them a key target for therapeutic interventions 7

Specific GPCR Targets

• Serotonin receptors are an example of GPCRs that can be targeted by agonists, such as psychedelic drugs, for transformative neuropsychiatric therapeutics 6
• Nonpsychedelic 5-HT2A receptor agonists may prove to be safe and rapidly acting antidepressants, highlighting the potential of targeting specific GPCRs for therapeutic benefits 6
• Other GPCRs, such as the MRGPR family of receptors, are understudied and may offer new opportunities for therapeutic interventions 6