After the Industrial Revolution, humanity saw a rise in the use of chemicals that revolutionized production. It was later that we found how detrimental they were to our health, but by the time we finally realized what was wrong, entire industries and their consumers depended upon those unhealthy chemicals, so it was difficult to outright stop them from existing. To combat this issue, researchers began exploring alternatives to these harmful chemicals, and with the advent of modern technology, they found these alternatives. One such alternative is the relatively new d9-caffeine, a variant of the common caffeine found in coffee.

The Basic Structure of d9-Caffeine

The d9-caffeine variant is much like the usual caffeine, the difference being between the chemical structure of the two. It is like a twin to regular caffeine and is similar to its counterpart. While regular caffeine consists of hydrogen atoms, in the d9 variant, this Hydrogen is replaced by Deuterium, an isotope of Hydrogen. An isotope is basically the same element but with extra neutrons. Such isotopes exist in nature and have been created by physicists in labs. The isotope of Hydrogen used in d9-caffeine, Deuterium, is identical to Hydrogen at the atomic level; the only difference is that while Hydrogen has no neutrons within the nucleus, the isotope Deuterium possesses a neutron within the nucleus.

Synthesizing the Wonder Chemical

Isotope Labeled Caffeine

Deuterium, also called heavy Hydrogen, is a stable isotope of Hydrogen found in ocean water and constitutes about 0.015% of all Hydrogen on Earth. The d9-caffeine is created via deuteration, a method that requires the substitution of Hydrogen with Deuterium within a molecule. This version is called the labeled isotope caffeine as it utilizes isotopes in its chemical bond.

Division of the Deuterium

As caffeine is an organic compound, it is way more complicated than a simple chemical compound. While other compounds are not intricate, organic chemicals like caffeine produce elaborate structures containing multiple rings together in a single structure that are not as easy to change. It may be difficult to change such structures, but not impossible to do so. All you must do is replace the Hydrogen atoms with the Deuterium in all the rings in the compound. 

Deuterium is introduced into the three methyl groups that make up caffeine. These groups exist at positions 1, 3, and 7. This results in 1, 3, 7-trideuteriomethyl xanthine-d9, thus the name d9-caffeine. This process yields a variant of caffeine with an almost identical chemical structure and physicochemical properties as regular caffeine but with modified pharmacokinetics.

The Pharmacokinetics of d9-Caffeine

What is Pharmacokinetics?

While some might be well versed in the more intricate side of science, a non-professional does not understand pharmacokinetics, so let us first examine what it is about. The science of chemicals being affected by the body when they pass through the body is pharmacokinetics, and the pharmacokinetics of a chemical means how that chemical is affected by the body. This includes the time it takes for absorption, bioavailability, distribution, metabolism, and excretion of that chemical.

Pharmacokinetics of d9-Caffeine

The pharmacokinetics of d9-caffeine were found to be much different from its counterpart. As per lab tests, the d9-caffeine stayed in the systems of the rats for longer, while the peak concentration remained the same as caffeine. d9-caffeine stayed in the rats for about 44-77% higher than caffeine. The d9-caffeine freely crosses the blood-brain barrier in rats.

Single-dose of d9-caffeine in humans exhibited a 29%–43% higher peak concentration while staying in their bodies for 4-5- times higher than caffeine and a 5-10-fold reduction in the exposure to active metabolites like paraxanthine, theobromine, theophylline of caffeine.

Unlike regular caffeine, d9-caffeine stays in the system longer, even when metabolized quickly. The effects last longer and at a more stable pace, while regular caffeine’s effects last longer for slower metabolization when compared to faster metabolization.

Pharmacodynamics of d9-Caffeine

Adenosine Receptor Affinity

Caffeine makes your brain active by blocking areas in your brain that are called adenosine receptors. These receptors work with a molecule, adenosine, that makes you feel sleepy. Caffeine prevents adenosine from doing its job, keeping you feeling awake and blocking these receptors. Caffeine also blocks other essential brain chemicals like dopamine (the happiness-inducing chemical of the brain) and glutamate (the energizer of the brain). d9-caffeine was tested for what it does to human adenosine receptors at the four receptor subtypes: A1, A2A, A2B, and A3. The test concluded that d9-caffeine has a similar adenosine receptor affinity as caffeine.

Published by: Nelly Chavez