Cevimeline Hydrochloride

Xerostomia, commonly known as dry mouth, is a significant complication in patients with Sjögren’s syndrome (SS), an autoimmune disorder primarily affecting the salivary glands. This comprehensive review discusses the various management strategies available to alleviate xerostomia symptoms, including pharmacological and non-pharmacological approaches. Pharmacological treatments, such as cholinergic agents (pilocarpine and cevimeline), have shown effectiveness in stimulating salivary secretion, while topical therapies, like saliva substitutes, provide temporary relief. Non-pharmacological methods, including salivary gland stimulation through chewing gum and dietary modifications, offer additional symptom control. Emerging therapies, such as gene and stem cell therapy, hold promise for future treatment. A multimodal approach tailored to the individual needs of the patient is essential for the optimal management of xerostomia in SS, ultimately improving patients’ quality of life. The review highlights the importance of ongoing research into novel therapeutic approaches to enhance treatment outcomes.

This review explores the main aspects that form the basis of the cholinergic-oriented treatment of Alzheimer disease. Muscarinic acetylcholine receptor subtypes in the brain and periphery are discussed. It includes a new and updated overview of the involvement of muscarinic receptors in Alzheimer disease and the recent development of new and highly selective M1 muscarinic receptor agonists with disease-modifying potential. Activation of the M1 muscarinic receptor is a rational therapeutic strategy for the treatment of schizophrenia and Alzheimer disease, as this receptor plays a pivotal role in modulating cognitive deficits and the pathology of the disease. Such activation can be achieved through M1 allosteric and bitopic muscarinic agonists, M1 positive allosteric modulators (M1 PAMs), and direct-acting M1 muscarinic orthosteric agonists. The efficacy of M1 PAMs depends on acetylcholine, which declines in Alzheimer disease as postsynaptic neurons lose cholinergic input from the basal forebrain. On the other hand, the activity of M1 muscarinic orthosteric agonists is independent of the functional or anatomic integrity of presynaptic cholinergic terminals, and likely retain efficacy as the disease progresses, even after presynaptic degeneration of cholinergic fibers. Based on the acceptance criteria for a preferred M1 muscarinic agonist for the treatment of AD, aiming for efficacy, specificity, and safety in clinical use, few M1 muscarinic agonists fulfill these requirements, such as orthosteric M1 agonists-cevimeline (aka AF102B), the first FDA-approved M1 agonist, and NSC001 (aka AF267B). The pros and cons of various muscarinic agonists developed are critically discussed in comparison to these drugs. The review proposes new alternatives to cholinergic therapy, particularly selective M1 muscarinic drugs, that should be designed to amplify its clinical effect and supplement the disease-modifying effect of new treatments to slow down or arrest disease progression.