Mesoridazine besylate

Names

[ Name ]:
Mesoridazine besylate

[Synonym ]:
benzenesulfonic acid,10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfinylphenothiazine
10-[2-(1-Methyl-2-piperidinyl)ethyl]-2-(methylsulfinyl)-10H-phenothiazine
Mesoridazine benzenesulfonate

Biological Activity

[Description]:

Mesoridazine (TPS-23) benzenesulfonate, a metabolite of Thioridazine (HY-B0965A), acts as an orally active phenothiazine antipsychotic agent. Mesoridazine benzenesulfonate is a potent and rapid open-channel blocker of human ether-a-go-go related gene (hERG) channels and blocks hERG currents with an IC50 of 550 nM (at 0 mV) in human embryonic kidney 293 cells[1].Mesoridazine benzenesulfonate can be used for the research of schizophrenia, as well as certain other psychiatric disorders[1][2].

[Related Catalog]:

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

[In Vitro]

Mesoridazine blocks human ether-a-go-go-related gene (HERG) currents in a concentration-dependent manner (IC50 = 550 nM at 0 mV), block increased significantly over the voltage range where HERG activates and saturates at voltages eliciting maximal HERG channel activation[1]. Mesoridazine (15 mM; 24 h) shows total absorption of 15.94 ± 4.04% and 39.24 ± 5.11% in nude mouse and pig skin, respectively[3].

[In Vivo]

Mesoridazine (15 mM; topical administration; once or daily for 7 consecutive days) displays potent activity and a long period of analgesia at blocking cutaneous pain[3]. Mesoridazine (15 mM) shows intradermal concentration of 0.34 0.74 nmol/mg after topical application on nude mouse back for 6 h[3]. Animal Model: Eight-week-old female nude mice[3] Dosage: 15 mM Administration: Topical administration, once (analgesia test) or daily for 7 consecutive days (irritation test) Result: Showed analgesic effect. A slight transepidermal water loss (TEWL) increased from 7.8 to 9.9 g/m2/h was observed.

[References]

[1]. Zhi Su, et al. Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel. J Mol Cell Cardiol. 2004 Jan;36(1):151-60.

[2]. I S M Salih, et al. Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. Clin Pharmacol Ther. 2007 Nov;82(5):548-54.

[3]. Liu KS, et al. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

Chemical & Physical Properties

[ Boiling Point ]:
570.5ºC at 760mmHg

[ Molecular Formula ]:
C₂₇H₃₂N₂O₄S₃

[ Molecular Weight ]:
544.74900

[ Flash Point ]:
298.9ºC

[ Exact Mass ]:
544.15200

[ PSA ]:
130.81000

[ LogP ]:
7.78380

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DB7176700

CAS REGISTRY NUMBER :: 32672-69-8

LAST UPDATED :: 199504

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C21-H26-N2-O-S2.C6-H6-O3-S

MOLECULAR WEIGHT :: 544.79

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction) Cardiac - other changes Nutritional and Gross Metabolic - changes in calcium

REFERENCE :: AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 17,1074,1988 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6153 No. of Facilities: 92 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 4525 (estimated) No. of Female Employees: 4107 (estimated)

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
22

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
DB7176700

Articles

Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.

Eur. J. Clin. Pharmacol. 59 , 45-50, (2003)

Approximately 7% of Caucasians have genetically impaired activity of the cytochrome P450 enzyme CYP2D6 and are classified as poor metabolizers (PM). The disposition of thioridazine has been related to...

Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.

J. Pharmacol. Exp. Ther. 299 , 83-89, (2001)

Atypical antipsychotic drugs, which are distinguished from typical antipsychotic drugs by a lower incidence of extra-pyramidal side effects and less propensity to elevate serum prolactin levels (e.g.,...