Cevimeline hydrochloride hemihydrate

Names

[ Name ]:
Cevimeline hydrochloride hemihydrate

[Synonym ]:
Spiro[1-azabicyclo[2.2.2]octane-3,5'-[1,3]oxathiolane], 2'-methyl-, (3R)-, hydrochloride, hydrate (2:2:1)
cis-2-Methylspiro(1,3-oxathiolane-5,3')quinuclidine hydrochloride hydrate (2:2:1)
Unii-p81Q6V85np
(+/-)-cis-2-Methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride hemihydrate
cevimeline hydrochloride
(2R,2'R)-2'-Methylspiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxathiolane] hydrochloride hydrate (2:2:1)
CeviMeline hydrochloride heMihydrates
Cevimeline hydrochloride hemihydrate
(2R)-2'-Methylspiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxathiolane] hydrochloride hydrate (2:2:1)
Spiro[1-azabicyclo[2.2.2]octane-3,5'-[1,3]oxathiolane], 2'-methyl-, (2'R,3R)-, hydrochloride, hydrate (2:2:1)
(+/-)-cis-2-methylspiro[1,2-oxathiolane-5,3'-quinclidine] monohydrochloride
Cevimeline HCl 1/2H2o
(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride
(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine]monohydrochloride hemihydrate
CevimelineHCl
Cevimeline (hydrochloride hemihydrate)

Biological Activity

[Description]:

Cevimeline hydrochloride hemihydrate, a novel muscarinic receptor agonist, is a candidate therapeutic drug for xerostomia in Sjogren's syndrome. IC50 value:Target: mAChRThe general pharmacol. properties of this drug on the gastrointestinal, urinary, and reproductive systems and other tissues were investigated in mice, rats, guinea pigs, rabbits, and dogs. The in vitro metab. of SNI-2011 was also evaluated with rat and dog liver microsomes. After oral administration, plasma concns. of SNI-2011 reached to Cmax within 1 h in both species, suggesting that SNI-2011 was quickly absorbed, and then decreased with a t1/2 of 0.4-1.1 h. The bioavailability was 50% and 30% in rats and dogs, resp. Major metabolites in plasma were both S- and N-oxidized metabolites in rats and only N-oxidized metabolite in dogs, indicating that a large species difference was obsd. in the metab. of SNI-2011. Sex difference was also obsd. in the pharmacokinetics of SNI-2011 in rats, but not in dogs. In the in vitro study, chem. inhibition and pH-dependent studies revealed that the sulfoxidn. and N-oxidn. of SNI-2011 were mediated by cytochrome P 450 (CYP) and flavin-contg. monooxygenase (FMO), resp., in both species. In addn., CYP2D and CYP3A were mainly responsible for the sulfoxidn. in rat liver microsomes.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[References]

[1]. Iga Y, Arisawa H, Ogane N, Saito Y, Tomizuka T, Nakagawa-Yagi Y, Masunaga H, Yasuda H, Miyata N. (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions

[2]. Omori Y, Asari T, Maruyama K, Kusama H, Kojima M, Shibata N. Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation. Arzneimittelforschung. 2003;53(5):342-50.

[3]. Washio, Takuo; Kohsaka, Kazuhiro; Arisawa, Hirohiko; et al.Pharmacokinetics and metabolism of radiolabeled SNI-2011, a novel muscarinic receptor agonist, in healthy volunteers: Comprehensive understanding of absorption, metabolism and excretion using radi

[4]. Washio, Takuo; Kohsaka, Kazuhiro; Arisawa, Hirohiko; et al.Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs.Arzneimittel-Forschung (2003), 53(1), 26-33.

[5]. Arisawa, Hirohiko; Fukui, Kenji; Imai, Eiichi; et al.General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjogren's syndrome. Arzneimittel-Forschung (2002), 52(4), 225-232.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.19g/cm3

[ Boiling Point ]:
308.5ºC at 760mmHg

[ Molecular Formula ]:
C₂₀H₃₅ClN₂O₂S₂

[ Molecular Weight ]:
435.09

[ Flash Point ]:
140.4ºC

[ PSA ]:
84.77000

[ LogP ]:
4.53590

[ Vapour Pressure ]:
0.000676mmHg at 25°C

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: WG9634812

CAS REGISTRY NUMBER :: 153504-70-2

LAST UPDATED :: 199703

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C10-H17-N-O-S.Cl-H.1/2H2-O

MOLECULAR WEIGHT :: 244.78

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 139 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5340821

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5340821

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40800 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5340821

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ RIDADR ]:
UN 2811 6.1 / PGIII

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Effects of pilocarpine and cevimeline on Ca2+ mobilization in rat parotid acini and ducts.

J. Med. Invest. 56 Suppl , 375, (2009)

Previous reports suggested that there is no significant difference in the binding affinity of pilocarpine and cevimeline on muscarinic receptors (1). However, in vivo studies from our laboratory sugge...

Cevimeline enhances the excitability of rat superior salivatory neurons.

J. Med. Invest. 56 Suppl , 267-9, (2009)

Cevimeline, a therapeutic drug for xerostomia, is an agonist of muscarinic acetylcholine receptors (mAChRs), and directly stimulates the peripheral mAChRs of the salivary glands. Since cevimeline is d...