Membrane Proteins Role in the Distribution of Drugs

Membrane proteins are the target of most drugs currently on the market due to their relationship with the vast majority of diseases they are designed to treat. Image Credit: sciencepics/ Drug activity depends on numerous factors such as absorption, excretion, distribution, and metabolism. Membrane proteins impact all such factors, making […]

Membrane proteins are the target of most drugs currently on the market due to their relationship with the vast majority of diseases they are designed to treat.

Membrane Proteins

Image Credit: sciencepics/

Drug activity depends on numerous factors such as absorption, excretion, distribution, and metabolism. Membrane proteins impact all such factors, making them important to consider when developing new drugs as their interaction with the substance helps determine its efficacy.

Membrane proteins are becoming increasingly recognized as having a vital role in drug distribution. The success of delivering a substance to a particular organ to guarantee its therapeutic effect hinges on the affinity of the drug with particular transport systems. Membrane proteins are key features of these transport systems, placing them at center stage for the ongoing development of new pharmaceuticals.

Here, we discuss how membrane proteins impact drug distribution and what this means for the future of drug development.

Membrane proteins facilitate and inhibit drug distribution

Drug transporter proteins are membrane proteins that exist in a range of tissues including the intestine, kidney, liver, lymphocytes, placenta, testis, and tissues that make up the central nervous system (CNS). These transporters are known to play a vital role in not only drug absorption, but also drug distribution. Drug transporter proteins are particularly important in the distribution of drugs to organs that are protected by blood-organ barriers.

Membrane transporter systems, which encompass membrane proteins, work together with the blood-brain barrier and the blood-cerebrospinal barrier as gatekeepers to the CNS. This makes membrane proteins particularly essential to the distribution of drugs that are administered to affect tissues of the CNS.

Distribution of pharmaceuticals to target organs and tissues is impacted by membrane transporters which either have the impact of enhancing or restricting distribution. Those that enhance distribution are classed as influx (uptake) transporters and those that restrict distribution are classed as efflux (export) transporters.

The mechanism of transporter proteins

Transporter proteins have not always been the focus of pharmacokinetic studies. Previously, research focused on the role of enzymes responsible for metabolizing drugs, as these proteins were considered to be the main determinants of drug distribution. However, new evidence has revealed how transporter proteins function alongside enzymes to facilitate or inhibit drug distribution.

Enzymatic reactions are classed as either phase II or phase II. Phase I reactions work by altering the chemical structure of the drug compound, resulting in augmenting or degrading its pharmacological activity. Phase II enzymatic reactions then conjugate the metabolites of phase I reactions with molecules containing hydrophilic functional groups.

Drug membrane transporters facilitate phase I enzymatic reactions by allowing drug compounds access to phase I enzymes. They also facilitate phase II interactions by helping to transport xenobiotics/metabolites towards excretion.

This relationship between membrane transporter proteins and drug-metabolizing enzymes is key to the distribution of pharmaceutical compounds to the brain and other tissues within the CNS.

The role of membrane proteins in drug development

Because of the pivotal role membrane transporter proteins play in drug distribution, studying their activity and interaction with new pharmaceutical compounds is paramount to developing the safety and efficacy profiles of new drugs. However, drug interactions with membrane proteins have been challenging to study.

Cell membranes are complex structures featuring a myriad of different elements such as carbohydrates, lipids, and proteins. This complexity can make it difficult to study the specific features of the membrane. Additionally, transporter proteins are too unstable to be studied outside of the membrane as they generally denture once separated.

The difficulty of studying membrane proteins has acted as a barrier to drug development, preventing scientists from gaining deeper insights into their interactions with pharmaceutical compounds and their impact on drug structure and function.

Recently, researchers have developed a mechanism that allows membrane proteins to be studied in greater detail. Biomimetic model membrane systems have been created as a platform for studying the behavior of membrane proteins. These systems have become increasingly valuable in vitro tools that allow scientists to study membranes in a controlled environment. While the systems do not mimic all the properties found in a natural membrane, specific characteristics required for test conditions can be effectively simulated using these models.

As a result, researchers are uncovering a more detailed view of the nature of membrane proteins and their influence on drug distribution. Examples of these model systems, such as vesicles or liposomes, Langmuir monolayers, solid-supported bilayers, and tethered bilayer lipid membranes, are being used to complement, rather than replace, studies using whole cells. In the future, these studies will likely provide a platform for preliminary screenings of drug–membrane interactions with new, exploratory compounds.

Overall, membrane proteins play a vital role in drug distribution, but their full impact is not fully known. As methodologies emerge that better facilitate the study of membranes, such as biomimetic model membrane systems, scientists will be able to gain deeper insights into the mechanism of action of these proteins.


  • Nature Reviews Drug Discovery, 2010. Membrane transporters in drug development. 9(3), pp.215-236.
  • Knobloch, J., Suhendro, D., Zieleniecki, J., Shapter, J., and Köper, I., 2015. Membrane–drug interactions studied using model membrane systems. Saudi Journal of Biological Sciences, 22(6), pp.714-718.
  • Swaan, P., 2003. Membrane Transport Proteins and Drug Transport. Burger’s Medicinal Chemistry and Drug Discovery,.
  • Yıldırım, M., Goh, K., Cusick, M., Barabási, A. and Vidal, M., 2007. Drug—target network. Nature Biotechnology, 25(10), pp.1119-1126.
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