Membrane Interactivity Shared by Receptor- Acting Drugs

Background: Although lipids have been regarded as a passive component to constitute biomembranes, they can also play an important role in modulation of the activity or function of membrane-embedded proteins like receptors. Membrane lipids are presumed to be one of additional sites of action for receptor-acting drugs because their broad pharmacological spectra are not necessarily interpretable by the direct action on receptors. In order to obtain novel insights into the drug target and mechanism, we reviewed the membrane interactivity of different classes of drugs to act on representative receptors.

Methods: A search of the scientific articles published between 1979 and 2018 was carried out by using PubMed/MEDLINE, Google Scholar and ACS Publications. The relevant research papers published in recognized international journals and on-line journals in English were preferred, but the review articles of specific importance were also included, although non-English language citations were excluded. Collected articles were reviewed by title, abstract and text for relevance with preference to more recent publications.

Results: Results of the literature search indicate that membrane interactivity is shared by various drugs that act on α- and β-adrenergic, muscarinic and nicotinic acetylcholine, γ-aminobutyric acid type A, N-methyl-D-aspartate, opioid and transient receptor potential vanilloid type-1 receptors. These receptor agonists and antagonists not only interact with receptor proteins but also would structure-specifically interact with membrane lipids to affect receptors by modifying the lipid bilayer environments surrounding them with the resultant conformational change of receptor proteins.

Conclusion: The structure-specific membrane interaction is pharmacologically contributable to diverse effects of receptor-acting drugs.