The Use of Esterase Inhibitors

Abstract

The increase in life expectancy of the population brought the emergence of age-related diseases, becoming a problem for public health. It currently presents an important growth of dementias, with emphasis on the most prevalent dementia of the type Alzheimer’s disease, characterized by the impairment of cognitive functions, affecting the mental state such as language, memory, attention, skills, and also the behavior and daily activities. We know that there is no cure for Alzheimer’s disease, but there are treatments that can change the progression of the disease. These treatments can be pharmacological and non-pharmacological, starting with drug cholinesterase inhibitors, in the early stages and intermediates of the disease, and drugs with actions based on noncompetitive antagonism of glutamatergic receptors, when the disease is in the intermediate stages to advanced (Santos et al., Atenção farmacêutica em pacientes com Doença de Alzheimer. Expansão do conhecimento e inovaçãotecnológica no campo das ciênciasfarmacêuticas / organizadora Iara Lúcia Tescarollo. – Ponta Grossa, PR, Brasil: Atena, 2020). Cholinesterase inhibitor drugs (ChE-Is) are still considered to be the main approved drugs for the treatment of AD (Minett TSC, Bertolucci PHF, Rev Neurociências 8:11–14, 2000). The justification for their use is the hypothesis that cholinergic deficits occur during the disease and the inhibitors work by increasing the availability of acetylcholine in the synaptic cleft (ACh) through the inhibition of its main catalytic enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) (Forlenza Ver PsiqClín 32:137–48, 2005; Grossberg, Curr Ther Res 64:216–35, 2003). ChE-Is are the only therapeutic class of drugs developed that have produced significant cognitive improvement in AD patients and represent the most promising therapeutic agents since the late 1990s (Minett TSC, Bertolucci PHF, Rev Neurociências 8:11-14, 2000). In the treatment of AD, the combination of ChE-Is with NMDA receptor antagonists can bring more satisfactory results compared to non-pharmacological therapies. Rivastigmine, one of the ChE-Is, may reduce or eliminate the need to use other adjuvant drugs in AD treatment, such as psychotropics and others, but this will depend on the stage of the disease. Rivastigmine is well tolerated and improves cognition and participation in activities of daily living among patients in mild to moderately severe stages of AD (Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stähelin HB, Hartman R, Gharabawi M. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999;318(7184):633–8. https://doi.org/10.1136/bmj.318.7184.633. Erratum in: BMJ 2001;322(7300):1456. PMID: 10066203; PMCID: PMC27767).