AF 102A hydrochloride is a biochemical.

Cevimeline HCl is an agonist of cholinergic that binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can enhance the secretion of exocrine glands, such as salivary and sweat glands.

(+)-Cevimeline hydrochloride hemihydrate ((+)-SNI-2011), a potent muscarinic receptor agonist, stands as a promising therapeutic candidate for treating xerostomia in Sjogren's syndrome. This compound has demonstrated a broad pharmacological profile across various systems including gastrointestinal, urinary, and reproductive, in animal models such as mice, rats, guinea pigs, rabbits, and dogs. Its metabolism was assessed in vitro using rat and dog liver microsomes, revealing that (+)-SNI-2011 is rapidly absorbed with peak plasma concentrations (Cmax) reached within one hour post-oral administration, followed by a decline with a half-life (t1/2) ranging from 0.4 to 1.1 hours. Bioavailability was recorded at 50% in rats and 30% in dogs. Metabolic analysis indicated species-specific differences, with rats producing both S- and N-oxidized metabolites and dogs only producing N-oxidized metabolites. Additionally, sex-based differences in pharmacokinetics were observed in rats but not in dogs. The in vitro study highlighted the involvement of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in the sulfoxidation and N-oxidation of SNI-2011, respectively, with CYP2D and CYP3A being primarily responsible for sulfoxidation in rat liver microsomes.

Cevimeline hydrochloride hemihydrate is a novel muscarinic receptor agonist, used as a candidate therapeutic drug for xerostomia in Sjogren's syndrome.

Cevimeline hydrochloride hemihydrate ((-)-SNI-2011), a novel muscarinic receptor agonist, is being explored as a potential treatment for xerostomia in Sjogren's syndrome, exhibiting an IC50 value indicative of its affinity for mAChR. This compound's pharmacological effects on the gastrointestinal, urinary, and reproductive systems, alongside its impact on various tissues, were thoroughly examined in species including mice, rats, guinea pigs, rabbits, and dogs. The metabolic breakdown of (-)-SNI-2011 was studied in vitro using rat and dog liver microsomes to assess its biotransformation. Upon oral administration, peak plasma concentrations were reached within an hour in both rats and dogs, showcasing rapid absorption and a subsequent decrease in concentration with a half-life ranging from 0.4 to 1.1 hours. Bioavailability was noted at 50% in rats and 30% in dogs. Metabolic pathways highlighted significant species differences, with both S- and N-oxidized metabolites identified in rats, but only N-oxidized metabolites in dogs. Additionally, gender differences in pharmacokinetics were observed in rats but were absent in dogs. In vitro studies pinpointed the involvement of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in the metabolism of (-)-SNI-2011, specifically through sulfoxidation and N-oxidation processes, respectively. CYP2D and CYP3A were identified as the primary enzymes responsible for sulfoxidation in rat liver microsomes.

Cevimeline, a parasympathomimetic and muscarinic agonist, affects M1 and M3 receptors. Cevimeline has been shown to treat dry mouth and Sj gren's syndrome. It is also used to reduce Xerostomia symptoms and increase salivary flow in head and neck cancer survivors after radiotherapy.