CEVIMELINE, HYDROCHLORIDE SALT

Absorption

Rapidly absorbed with peak concentration after 1.5 to 2 hours

Chemical properties

Off-White Solid

The Uses of CEVIMELINE, HYDROCHLORIDE SALT

A muscarinic M1 and M3 receptor agonist. Sialagogue

Background

Cevimeline is a parasympathomimetic agent that act as an agonist at the muscarinic acetylcholine receptors M1 and M3. It is indicated by the Food and Drug Administration for the treatment of dry mouth associated with Sj?gren's syndrome.

Indications

For the treatment of symptoms of dry mouth in patients with Sj?gren's Syndrome.

Biological Activity

cevimeline is a muscarinic receptor agonist especially on the m1 and m3 receptors. [1]cevimeline has been approved for use against symptoms of dry mouth by activating the m3 receptors of the parasympathetic nervous system. cevimeline is effective and safe in improving symptoms of dry eye with 20 mg three times per day [2]. cevimeline increased the intracellular ca+ level in parotid gland acinar cells over 1 μm and rat, enhanced the excitability via muscarinic receptors, thereby, cevimeline alleviates dry mouth symptoms by stimulating secretion by the salivary glands. cevimeline has a longer duration of salivation[3]. cevimeline plays a part in alzheimer’s disease. cevimeline decreased aβ (1–40) level in the cerebrospinal fluid (csf) at 1 mg/kg without changing α-apps in rabbit and significantly decreased csf aβ in ad patients.[4]

Pharmacokinetics

Cevimeline is a cholinergic agonist which binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands and increase tone of the smooth muscle in the gastrointestinal and urinary tracts.

Metabolism

Primarily hepatic, isozymes CYP2D6 and CYP3A4 are responsible for the metabolism of cevimeline. Approximately 44.5% of the drug is converted to cis and trans-sulfoxide, 22.3% to glucuronic acid conjugate, and 4% to N-oxide of cevimeline. Approximately 8% of the trans-sulfoxide metabolite is then converted into the corresponding glucuronic acid conjugate.

References

1. f. b. vivino, i. al-hashimi, z. khan, f. g. leveque, p. l. salisbury, 3rd, t. k. tran-johnson, c. c. muscoplat, m. trivedi, b. goldlust and s. c. gallagher, arch intern med 1999, 159, 174-181. 2. m. ono, e. takamura, k. shinozaki, t. tsumura, t. hamano, y. yagi and k. tsubota, am j ophthalmol 2004, 138, 6-17. 3. k. ono, t. inagaki, t. iida, r. hosokawa and k. inenaga, j med invest 2009, 56 suppl, 375. 4. a. fisher, z. pittel, r. haring, n. bar-ner, m. kliger-spatz, n. natan, i. egozi, h. sonego, i. marcovitch and r. brandeis, j mol neurosci 2003, 20, 349-356.