Plant alkaloids and chemodefense

Although many alkaloids have toxicity which is immediate and topical so as to discourage predation, many alkaloids do get absorbed into the predator's body and can therefore produce pharmacological and toxicological effects beyond the point of exposure. Some of these effects are extreme and may cause severe reactions in the predator, again discouraging predation.

Animals learn to stay away from such plants. Alternatively, they develop protective mechanisms against the toxicological effects of the alkaloids. Apart from the biological membranes which provide an initial protective barrier against insoluble and hydrophilic chemicals, many organisms also have evolved protective mechanisms such as the cytochrome P450 enzyme systems and the efflux transport proteins to detoxify and repel the more permeable alkaloids which may be able to escape past the biological membranes. In response, plants, over time, evolve even more complex chemicals to overcome animal defense mechanisms. This plant-animal arms-race create the complex environment which now can be seen to determine pharmacokinetic behaviour of the the drugs we use.

Drug metabolism and drug transport must therefore be seen as component parts of an integrated process to protect animals from the toxicity of plant alkaloids.

Read this interesting account of the mustard oil bomb.

A well known groups of alkaloids are the methylxanthines.

Caffeine: R₁ = R₂ = R₃ = CH₃

Theobromine: R₁ = H, R₂ = R₃ = CH₃

Theophylline: R₁ = R₂ = CH₃, R₃ = H

The three main members are caffeine (1,3,7-trimethyxanthine), theobromine (3,7-dimethylxanthine) and theophylline (1,3-diethyxanthine). Caffeine is found in tea and coffee, while theobromine is the main methylxanthine found chocolate. The methylxanthines are phospohodiesterase inhibitors.

The metabolism of caffeine is shown below. Caffeine has been use as a probe substrate to develop metabolic ratios for CYP1A2 and N-acetytransferase 2.