ABSTRACT
The amount of approved drugs for the treatment of the symptoms of AD is limited. The main reason is the fact that the therapy is hypothesis driven, not causal. Five Food and Drug Administration (FDA) (United States) approved drugs are currently used for the treatment of AD symptoms. Four of them are acetylcholinesterase (AChE) inhibitors: donepezil, galantamine, rivastigmine, and tacrine. It has been observed that in patients suffering from AD, the amount of acetylcholine decreases mainly in the areas responsible for memory and cognition, for example, limbic and association cortices (cholinergic hypothesis of cognitive dysfunction) [4]. An interesting fact is that in AD patients, butyrylcholinesterase (BChE) becomes the predominant cholinesterase in the brain [4]. Therefore, the search for BChE inhibitors is equally important as looking for the new AChE inhibitors. Currently used drugs have several common side effects, which include nausea or vomiting. Muscle cramps, bradycardia, or decreased appetite appears less frequently in patients treated with AChE inhibitors. Donepezil is the only AChE inhibitor approved for use in the advanced stage of AD, contrary to others that are applied in mild and moderate AD. Other substances have been also identied as AChE inhibitors, just to mention huperzine A, lycoramine, sanguinine, protopine, palmatine, berberine, sanguinarine, terpenoids, and many others [5]. As far as terpenoids are considered, it has been shown that they are also potent free radical scavengers, which can be benecial in the treatment of neurodegenerative ailments, for example, AD [5,6]. Terpenoids seem to have a great potential for the treatment of AD symptoms. They are low-molecular lipophilic compounds that can easily penetrate the blood-brain barrier [7]. The side effects from the gastrointestinal tract can be excluded in the future, as terpenoids may be delivered in transdermal systems or could be inhaled and absorbed through the lungs [5,7]. The results of memory tests obtained by demented people also improved after regular administration of standardized Ginkgo biloba extract (EGb 761) [8]. Most recently, two substances have undergone clinical trials for their possible use in the treatment of AD symptoms, namely, latrepirdine and huperzine A [2]. Apart from inhibiting AChE and BChE, latrepirdine also inhibits the activation of NMDA receptors as well as acts as a neuroprotector [2]. Unfortunately, latrepirdine turned out to be ineffective in several clinical trials. Huperzine A, apart from being a selective AChE inhibitor, also reduces glutamate-induced cytotoxicity [2].
