Understanding the complex inner-workings of the human body is like trying to do an incredibly large puzzle. There are countless pieces that seem to have nothing to do with each other, but that all fit together and depend on one another for a complete functioning of the whole. This concept is particularly present in the search for effective drug therapies for diseases and illnesses of all kinds. One must understand not only how the drug affects the disease being targeted, but also how it subsequently affects the rest of the body; a drug is no good if it treats one condition but brings on another. This was the focus of a study done by Watabe et al. from the Osaka University Graduate School of Medicine. The role of Acetylcholinesterase (AChE) in bringing on conditions such as Alzheimer's Disease (AD) is well known. AChE is an enzyme that rapidly degrades acetylcholine (ACh) into chlorine and acetate. Since a progressive loss of cholinergic neurons is associated with the onset of AD, a variety of AChE inhibitors have been developed to try and mitigate this reaction with ACh and stave off AD. Of these inhibitors, donepezil (DNP), galantamine, and rivastigmine have been tested, with DNP being the most commonly used. While DNP has proven to be an effective AChE inhibitor, the complete range of side effects upon the rest of the body is still unknown.

Part of the reason for this has been the way in which the drug has been administered; microdose positron emission tomography (PET) allows for radiolabeled drugs to be administered in amounts far lower than what the dose would normally be. This allows for an effective study of the pharmokinetics of the drug, including the side effects of unexpected distribution to non-target organs. Up until now, research on DNP has focused on how it distributes within the brain. One study found that regionally administered DNP distributed heterogeneously in the brain. Another study found that intravenously administered DNP localizes in key parts of the brain, such as the striatum, thalamus, and cerebellum, where AChE can be found in high concentrations. The study did not, however, look at how DNP was interacting with the other organs in the body it reaches. Using the Amplite® Colorimetric Acetylcholinesterase Assay Kit, Watabe et al. were able to measure AChE activity in organs throughout the body, more specifically in the adrenal gland.

By making use of this assay kit, the research team was assuring themselves of having high-quality and reliable results. The assay kit uses DTNB to quantify the thiolcholine produced from the hydrolysis of acetylthiolcholine by AChE, and produces intense, highly-visible results. This is important in this type of study as accurately measuring AChE levels reflects potential adverse effects that the drug produces. In this case, Watabe and his team found that DNP does in fact accumulate in the adrenal gland, which suggests the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitor, revealing a previously unknown side effect. Achieving this result required careful and accurate analysis provided by tools, such as with the Amplite® Colorimetric Acetylcholinesterase Assay Kit, and helps to clear up the effectiveness of potential treatments for diseases such as AD, taking us one