Neuropharmacology of Cevimeline and Muscarinic Drugs-Focus on Cognition and Neurodegeneration.

Patrik Oleksak,Martin Valis,Jiri Patocka,Michal Novotny,Jan Pavlik,Blanka Klimova,Jakub Hort,Kamil Kuca,Eugenie Nepovimova

doi:10.3390/ijms22168908

Abstract

At present, Alzheimer’s disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer’s patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.

Highlights

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder that affects memory and thinking skills, and eventually, leads to the inability to execute the activities of daily living [1,2]
This type of memory includes three different types of memories, all of which are significantly impaired in later stages of AD: semantic memory associated with understanding the meaning of words, episodic referring to the past events, and procedural associated with an ability to carry out a task
Absorption: After peroral administration of a single dose (30 mg), cevimeline is rapidly absorbed with a mean time to peak concentration of 1.5 to 2 h

Summary

Introduction

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder that affects memory and thinking skills, and eventually, leads to the inability to execute the activities of daily living [1,2]. It is the fifth leading cause of death in the world [3] and the most common form of dementia, accounting for 60–70% of all dementias [4]. In the advanced stages of the disease, patients have problems with their long-term memory, i.e., the memory that refers to the storage of information over an extended period [5]. This type of memory includes three different types of memories, all of which are significantly impaired in later stages of AD: semantic memory associated with understanding the meaning of words, episodic referring to the past events, and procedural associated with an ability to carry out a task

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Conclusion